Fright Night Part II begins after the hellish events in the original Fright Night. Charley (William Ragsdale) now believes that Jerry Dandridge (Chris Sarandon), was nothing but a serial killer posing as a vampire. As a result, he comes to believe that vampires never existed.
Charley, along with his new girlfriend, Alex Young (Traci Lind), go to visit Peter Vincent (Roddy McDowall), who is again a burnt-out vampire killer on Fright Night much to the chagrin of the boy-who-cried-wolf Charley. It is while visiting Peter's apartment that Charley sees four coffins being taken into a car. On the way out from Peter's apartment, Charley sees four strange people walk past him, into an elevator. Charley instantly becomes smitten with one of the four, the alluring Regine (Julie Carmen). Charley drives Alex back to her dorm room and begins to make out with her, only to pull away and see Regine staring back at him. A ticked-off Alex storms off, not realizing that something is following her. Another girl leaves the dorm as Alex enters, and she is followed and killed by one of Regine's henchmen, Belle. Alex, meanwhile, is unaware that Louie, another of Regine's posse, is scaling up the wall outside her window, but he is startled and falls when Alex inadvertently slams her window shut on his hands. Bozworth ( Brian Thompson), the third heavy, makes fun of Louie before consuming some bugs.
Meanwhile, later that night Charley dreams that Regine comes to visit him, only for her to turn into a vampire and bite him. The next day Charley talks to his psychiatrist who assures him that what he dreamed was only natural. Alex finds Charley bowling, per doctor's orders, and Charley agrees to go to the symphony with her. On his way there however he sees his friend Richie (Merritt Butrick) with Regine and opts to follow him. Charley climbs up to a fire escape outside of Regine's apartment, only to be horrified when he sees Regine and Belle attack and drain Richie's blood. Charley runs off to find Peter, and the two of them arm themselves with crosses and crash Regine's party.
There, Charley finds Richie but is shocked to find him alive and well with no bite marks on his neck. Regine makes her entrance, doing an erotic dance with a mesmerized Charley. She introduces herself to Peter and Charley, and claims to be a performance artist in town for some shows. Satisfied that what he thought was Regine attacking Richie was nothing but an act, Charley leaves when he remembers his date with Alex; Peter elects to stay behind and partake in the debauchery. Peter notes that there are people in the corners of the room biting others on the neck, piquing his curiosity. Noting the odd behavior, he draws his pocket mirror and finds that Regine and Belle, who are dancing in the middle of the dance floor, cast no reflections.
Storming out of the party, Peter runs into Regine waiting for him outside. As he runs down the stairwell Peter again comes face-to-face with Regine, who reveals the "eternal secret": She is a vampire, the sister of Jerry Dandridge, and has come to take her revenge on both Charley and Peter. Peter runs back home and hides, resolving to tell Charley in the morning what has just transpired. Charley, meanwhile, blows off his date with Alex, returns home and falls asleep, only to be visited by Regine, who bites him on the neck while he sleeps.
Charley, content with the explanation that Regine is a performance artist who only pretends to be a vampire, once again is in denial. He begins to discuss the situation with Alex when Peter arrives to try and warn the couple about Regine but neither believe him. Peter states that he has warned them and runs back to his home, packs his belongings and departs.
Meanwhile, Charley has started to become more of a vampire, becoming sensitive to garlic and sunlight. After failing to talk to his psychiatrist, he overhears a news report about his Richie's body being discovered the previous night. Now believing that everything is real, Charley goes to see Peter, only to find that Peter has gone.
Louie is once again stalking Alex and when Charley shows up he becomes physical. Louie reveals his true nature to Alex and Charley and stalks them in the school library, only to bust through a window and escape after Alex injures him by cramming wild roses into his mouth. Alex and Charley are then arrested by campus police. Peter, meanwhile, is also arrested after he shows up on the set of Fright Night and attempts to kill its new host, Regine, on live TV. Everyone thinks he's lost his sanity as he says, "I have to kill the vampire"; as a result, Peter ends up in a state hospital. Alex is bailed out by Charley's shrink and goes to post bail for Charley, only to find that he has already been bailed out by Regine.
Alex and Dr. Harrison are on the way to the state hospital when the doctor reveals that he is in fact a vampire. He tries to bite Alex only for her to turn the tables on him and run him through with a piece of wood. She then assumes his identity as a doctor and tries to get Peter released. At the hospital, a commotion allows Alex and Peter to escape.
Alex and Peter head to Regine's lair in order to save Charley. They find a disoriented Charley, who is slowly turning into a vampire. They rescue him from an undead Richie, and in the process manage to kill Belle, Bozworth and Louie before confronting Regine. She attempts to escape into her coffin, but finds that Charley has lined it with Communion wafers. Regine manages to knock Alex unconscious and attempts to turn Charley into a vampire, but Peter manages to destroys her with sunlight.
The following day, Charley and Alex discuss the previous day's events, with Alex joking that if she wrote a book about it, no one would ever believe them. They know that there are no more vampires, but acknowledge that they can never be 100% certain.