We begin with an aerial view of the hotels in Las Vegas, before settling on one called the Shangri-La. Inside one gaming area, the patrons all seem to be winning. Joe, a floor boss, picks up a phone and asks where Bernie is - they need him right away. Moments later, from an elevator emerges Bernie Lootz (William H. Macy), dressed in a seedy-looking ill-fitting suit. As he limps through the casino and passes people, their luck immediately goes sour. Roulette wheels, blackjack cards, crap tables and slot machines all stop paying out. Bernie then wanders over to Doris, the barmaid, who pours him a coffee. He asks for cream, but as she starts to pour it the creamer runs dry.
A pretty blonde waitress, Natalie Belisario (Maria Bello) brings a drink order to the bar. Bernie tries to chat with her, but she is clearly distracted. She asks Doris if Shelly left word for her; he was supposed to put her at the tables rather than the nickel slots she's been stuck at. As Natalie leaves, Bernie promises her he'll talk to Shelly but she doesn't seem to notice.
Joe tells Bernie he's needed on table 11. Bernie tells Joe to have Natalie bring him a drink - that he talked to Shelly and he wanted her on the tables tonight. Natalie brings him the drink, thanking him for talking to Shelly. Bernie then takes the drink to a player at the crap table who's having a hot streak - which ends immediately. Bernie then plays some blackjack, losing his money and wrecking the luck of all the other players.
Next, we see casino boss Shelly Kaplow (Alec Baldwin) in his office. He has a headache and is trying to get a manicure, when a small entourage of men in gray suits barge in . Leading the pack is his casino partner, Nicky Bonnatto (Arthur J. Nascarella). Nicky introduces Shelly to his new VP Larry Sokolov (Ron Livingston) and his numbers guy, Marty Goldfarb. After drinks, smokes and jokes, Nicky tells Shelly that Larry has some ideas to revitalize the Shangri-La. Shelly asks why - they raked in $35 million last year. Larry explains that he respects the job Shelly has done the last 16 years, but that things have changed on the strip. Shelly responds in disgust about the "Disneyland" the strip has become. What was once a high class hooker, has now become a cheap, fat whore. Larry points out that other casinos are raking in dough and the Shangri-La just can't compete anymore. Shelly says they're not trying to compete; this is where old-time real money comes to play. Larry counters they only offer nostalgia - fine for museums but not casinos.
Later, Shelly meets Bernie on the floor and stops him for a chat. He asks how his knee is and tells him about an orthopedist who can make a kneecap out of titanium. But Bernie reminds him he won't be here past Sunday. Shelly asks him where he's going to go that better than this. But Bernie insists that in seven days he's gone.
Bernie goes to his motel room at the Bettor Life motel, a dismal dive. He sits in bed watching TV. He can't even try to sleep because his neighbor is having loud, headboard-banging sex on the opposite side of the wall.
Next day, a high roller is on a hot streak. When Natalie brings him his drink, he deliberately takes his time stuffing the money into her cleavage, causing her to topple over into Bernie. She apologizes, but Bernie tells her she might want to stick around. He hands the guy some new dice, and his lucky streak evaporates. The roller sees Natalie smiling at his misfortune, and starts swearing at her, until he is hauled off by security. Natalie smiles at Bernie gratefully.
Shelly takes his partner and the new guys out to watch Buddy Stafford (Paul Sorvino), the casino's older, worn-down lounge singer. Larry is clearly not impressed. Shelly goes to see the singer in his dressing room. Buddy is embarrassed about his performance. Shelly tries to pump up his ego, but Buddy is more concerned whether Shelly brought his fix. Shelly did and Buddy quickly shoots up. He tells Shelly about a nature show he saw - how a lion who was once the leader of a pride had gone past his prime and was expelled and left to forage on his own until he died. It would be so much easier, he moans, if he could just walk away with his dignity intact. Shelly disagrees, saying that would be like admitting he was dead already.
Bernie walks out to his car and is surprised to find Natalie waiting for him. "Buy you a drink?" she invites. Larry, meanwhile, introduces Shelly to Johnny Capella (Joey Fatone), a new hot singer he thinks should be headlining at the Shangri-La. Shelly tells Larry he already has Buddy signed up for five more years. Johnny is miffed and walks out.
Natalie and Bernie are in a diner, where she is reviewing his astrological chart, telling him he is a slow starter when it comes to romance. He tells her it all doesn't matter; he knows what the outcome will be - all bad. He asks if she knows what he does. "You're a cooler", she replies. "You turn winners into losers". He tells her he does it by just being himself. Everyone who's ever been next to him has had their luck turn sour; it's always been that way. That sounds like a self-fulfilling prophecy, she retorts. He blurts out that he is leaving in five days anyway, so she suggests they don't waste any time and just go to his place. He nervously tells her he's not sure he can afford her. She is insulted, and he realizes he's made a mistake. I've done it again, he tells her. I've cooled the damn table. But she assures him he hasn't cooled anything yet.
They go to his motel room, where she notices his plants are all dead, and he has a cat food dish but no cat. She sits down on the bed, while he dusts off an old record. But as it starts to play the needle scratches across it. He resets it and nervously sits next to her. She tells him to relax - at least one of them has done this before. As the record starts to play, "Luck Be a Lady Tonight", she starts to undress. He notices she has a tattoo of two dice, each reading a two, on her behind. She walks to him coyly and starts to seduce him. But he is nervous, and ends up just rolling on top of her and finishing very quickly. She tells him gently, "It's okay. I've had worse", then gives him other kind reassurances. The next morning Bernie wakes up to find he's alone. Sadly, he picks up her pillow and hugs it. Suddenly she walks out of the bathroom, brushing her teeth, and asks if he wants to go to breakfast. He nods yes with a huge smile.
At breakfast, he tells her about his past. He was an out-of-control gambler who built up a huge debt until Shelly broke his legs with a baseball bat. Natalie is horrified, but Bernie says he's actually grateful. His shattered bones are a reminder to keep him from giving into the temptation to gamble. He worked out a repayment plan with Shelly - six years off the books cooling tables, and it's up in five days. The conversation is interrupted as a pregnant girl nearby has labor pains. Bernie sees them and recognizes the husband as his son, Mikey (Shawn Hatosy). Bernie and Natalie escort the pregnant couple, Mikey and Charlene (Estella Warren), to their car. She has settled down and is no longer in labor. When Bernie asks about Mikey's mother, he angrily responds she's getting by as long as she's high. Bernie nervously invites him to come to his motel to "catch up". Mikey says he might do that for the kid's sake.
Bernie sits down at a blackjack table with one other player, Mel, who is obviously winning. He bets one hand and the dealer goes bust with it. Afterward, incredibly, the dealer busts on hand after hand, letting Mel rake in the dough. Bernie is perplexed and leaves the table. Shelly wonders if the dealer is cheating, but can't believe it. They run across Larry - who knows Bernie is a cooler. He chides Shelly for sticking to the old ways. He says there are more effective ways nowadays. He shows Shelly a CD with soft music laced with a subliminal message of "Lose. Lose. Lose." Shelly only rolls his eyes.
The other partners arrive, and Shelly takes them to Buddy's room only to find Buddy on the floor dead of an overdose. Shelly suggests that the Paradise room stay closed tonight in Buddy's honor, but Larry quickly has Johnny Capella take over and do the show. The partners are impressed, but not Shelly.
Bernie and Natalie try the ring toss as a carnival, but she misses all her tosses. They sit down and Natalie looks sadly at a little boy standing next to his dad. She asks Bernie if he noticed the tattoo on her butt: two dice each with a 2 - a Little Joe. She admits she had a son named Joe, but only for a year. She gave him up for adoption ten years ago because she was 17 and wanted her life back. Her family abandoned her after that, and she ran off to become a showgirl. Deep down, she knows she did the right thing, but now feels she was selfish. Bernie stands up as if to leave, and tells her softly, "I think...I could kick your ass at the dime toss". She laughs and they hug tenderly.
Afterward, they make love in his motel room. Bernie is now very confident and gives Natalie obvious pleasure. Then with a smile he asks if she'll do something for him. Moments later, it sounds like they are having loud, headboard-banging sex, but the camera pans up to reveal that the two of them are just leaning against the headboard, rocking it and screaming out loudly. Finally, Bernie screams out and the two collapse, quietly laughing as the neighbor yells for them to shut up. "Did we wake you?" Bernie calls out.
Later on, Natalie returns to Bernie's apartment to find Charlene and Mikey waiting there. Mikey asks if Bernie is renting her, because he can't figure out how else his loser father could get so lucky. Before she can say something back, Bernie returns from parking his car. He's surprised but happy to see Mikey. Mikey then tells him they're strapped for money and Bernie gives them $3,000 in cash, all the money he has to spare.
Meanwhile, Larry presents a model of the new Golden Shangri-La to the partners: 3 floors of gaming, entertainment, boutiques, restaurants - even a roller coaster. Shelly responds by telling them the plot of the movie LOST HORIZON, how Shangri-La was totally untouched by the outside world - a paradise. Thats what the hotel Shangri-La was supposed to be, and you don't mess with that. Shelly insists that someday people will want the old Vegas back and he'll be there to give it to them.
Nicky then goes to play some craps but is annoyed by a rude player. After Nick craps out and the guy laughs, Nicky head-butts him and beats him bloody until security, called by Bernie, drags the guy away. Bernie tells Natalie how anxious he is to get out of Vegas and begs her to come with him. She answers that she's done an astrological compatibility chart on them and they're good together - but only if they stay in Vegas.
Bernie returns to his job. As he stands by a table, he is appalled to see his son there, playing craps. Natalie finds him and so does Larry, as Mikey rolls two nines and wins big. Shelly arrives in time to see Mike subtly switching back the real dice for his obviously loaded dice. He then throws a losing roll and decides to graciously leave with his winnings. Shelly tells him he doesn't want to lay out that kind of cash on the floor and invites them to come to his office to collect. Mikey agrees, but when Shelly tells him not to bother bringing his chips he knows he's in trouble. Larry suggests they turn them in to the authorities, but Shelly tells Larry to watch him protect his investment the "old school" way. Bernie is torn up, but goes to save his son.
Shelly has the couple down in a basement area, about to work Mikey over when Bernie arrives and begs him to stop. Shelly accuses Bernie of being in on the con, but believes him when he denies it. Instead, he tells Bernie they were up 150 grand when they left the table, so he wants $75,000 each for their lives. When they start to punch Mikey, Bernie agrees to cover the 150 G's. Charlene then starts to have contractions and pleads to go to the hospital. Shelly responds by kicking her in the stomach, then pulling up her shirt to reveal that the "baby" was just a large cushion. Shelly mocks the shocked Bernie by cradling the cushion. He gives Bernie a chance to change his mind but the cooler still offers to cover the debt. Shelly then orders Mikey to be put up on the table. Bernie pleads that they had a deal, but Shelly tells him 150 grand buys only their lives. With that he takes a sledge hammer and breaks both of Mikey's legs.
Back at his motel, Bernie blames himself for what happened to Mikey. Natalie gently tells him to stop beating up on himself and begins to dance with him instead. Later on, they are in bed together. She sits up and confesses that she knows she loves him. "You blindsided me, Bernie Lootz," she declares. "I never saw it coming". She then tells him there are things about her that he should know, but he doesn't care; it won't change how he feels about her. He's afraid to voice just how he feels about her because of all his rotten luck. But she tells him his rotten luck is all over now, so he admits that he loves her too.
As a new day dawns, Bernie awakes to find his cat Trixie has come back, and Natalie has left him a note, "Have a Spectacular Day". He goes off to work with a new confidence. When the waitress pours his coffee, the creamer finally pours out cream for him. As he makes his rounds, people around him start to get very lucky. Even as Shelly takes him aside to find out what's going on, a brand new slot machine rigged for virtually no payouts hits a big jackpot. Bernie tells Shelly theres nothing wrong with him - he's just in love!
Shelly has Natalie brought to him. He reminds her he only hired her to be a lover to Bernie, not to actually fall in love with him. Now his falling in love has turned Lootz's bad luck to good and cost the casino at least a million. He demands that she leave him, not even telling him to his face but just leaving a note. She refuses at first until Shelly threatens her life.
Bernie returns home to find a note from Natalie that she has left him. Afterward he returns to the casino to find the creamer has run dry again and he is once more bringing bad luck to everyone he touches. He meets Shelly in the lounge and asks if he muscled Natalie into leaving, but Shelly denies everything and acts offended. Bernie comments that the new lounge singer is all flash and no soul and that he misses Buddy. Shelly tells him Buddy was tired and that he gave him an easy way out. He admits that he knew Buddy would never accept the casino buyout. He'd have fought to the end and eventually would have been hurt. So he gave him the overdose instead and let him die peacefully. Bernie is appalled.
That night in his motel room, a lonely Bernie hears a knock on the door. Natalie is back, suitcase in hand. He takes her back before she can even say a word. Later, in bed, she suggests they run away together, but he says he can't. He owes Shelly a debt, and if he ran, Shelly would come after him and hurt her as well.
At the casino, Bernie is bringing people luck again, so Shelly has Natalie grabbed from the motel. He tells her he could make her disappear and no one would miss her. "Bernie would!" she counters. She tells Shelly it must kill him to know that Bernie loves her. Bernie was your friend, she shouts at him, and you crippled him. Still he stood by you but no more! She and Bernie are leaving tonight and he can't stop them. Shelly slams her face into a mirror which shatters and leaves her face bloody. He then departs quietly.
Bernie returns home to find Natalie hiding in the dark. He finds the broken mirror and turns on the light, seeing her with cuts on her face. She confesses that Shelly paid her to get close to him. She thought it was easy money. But as she got to know him, she saw that he wasn't a phony or a hustler but a decent guy. And she loved the way he treated her like a lady. Now Shelly wants her gone because she brought him luck. She just wanted to tell him the truth before leaving him, because she knows he wouldn't want her now. But instead, Bernie rushes her to the hospital, where they stitch up her cuts. He tells her afterward that everything will be all right. And if she ever looks in the mirror and doesn't like what she sees, then don't believe it. Look into my eyes instead, he tells her tenderly, they're the only mirror you're ever going to need.
They go back to the Shangri-La. She tells him she lied about his astrological chart that first night - that it was actually the worst she had ever seen. But he assures her that was before he opened his heart to her now he has Lady Luck on his side. She gives him the $3,000 that Shelly had paid her and suggests he give it to Shelly as a down payment.
He goes inside to where Shelly is meeting with his partners, throws Natalie's bloody handkerchief on the table and punches Shelly in the stomach swearing to kill him if he touches Natalie again. Shelly and his men drag Bernie up to the roof. Shelly says he hurt Natalie because he never gives up on a good thing, and Bernie is a very good thing - the best cooler ever. Bernie says he's not that man anymore. He promises to leave, get a job and send Shelly half his paycheck, but.Shelly says if he tries to leave the casino without paying his debt, he'll toss both he and Natalie off the roof. Bernie says he won't do that, because with him dead, he'd no longer the biggest loser in the world - Shelly would. What do you have except this place, Bernie challenges, your legacy is an illusion - you've got nothing. Shelly isn't impressed by the speech and walks away.
Bernie turns his $3,000 into chips and starts throwing the dice at the crap table and winning. After he has run up some serious money and gotten Shelly's attention (but no interference from him) Larry arrives demanding Shelly shut him down right now and proclaiming that Bernie isn't leaving with one dime. Shelly hauls Larry into the men's room and tells him Bernie is okay and nobody's touching a hair on his head. He pins Shelly down and declares, wait, on a subsonic level, I hear a mantra "Pain! Pain! Pain!" Then he breaks Larry's wrist.
At the table, Bernie is up over 100 grand until he craps out. He bets again but craps out a second time. He then takes the rest of his chips - $80,000 in all and places one last bet, throwing the dice nervously. He is next seen walking out of the casino empty-handed. Natalie is just grateful that he is alive as he drives them away. Meanwhile, Shelly is in his office with a headache, refusing to answer his ringing phone. He finally smashes the model of the new Golden Shangri-La to bits.
Miles away in the car, Natalie asks Bernie to tell her what happened. He stops the car on the side of a desert road and opens the door as if he has to throw up. Meanwhile, Shelly gets into his car in the parking lot only to find Nicky waiting in his back seat. Bernie, meanwhile, proceeds to pull wads of money out of his pockets. He tells Natalie he won big at the casino. "Bahamas, here we come", he declares. Then a cop appears at their window, ordering them to step out. Bernie tells the cop he's sorry if he was driving carelessly, but that they just won a load of money. The cop pulls out a gun and tells them they didn't win anything - and orders them to get on their knees.
Nicky tells Shelly he's just protecting his investment the old school way. He points his gun at Shelly's temple and shoots him dead. Meanwhile, on their knees in the desert, Natalie whispers to Bernie that they should have known it was all too good to be true. They turn to give each other one last loving gaze as the cop cocks his gun. But instead of hearing a gunshot, they hear a loud thud. They turn to see that a car has run down and killed the cop. Bernie realizes it was just a random drunk driver - a freaky, lucky coincidence. Bernie and Natalie get back into the car and drive away with their money.
We see Larry being introduced to the investors as the new Director of Casino Operations at the new Golden Shangri-La. "The future looks very bright, gentlemen. Very, very bright," he assures them. And with those words of endorsement ringing in our ears, we watch Bernie and Natalie drive off toward a new life together.