- In a world where supervillains are commonplace, two estranged childhood best friends reunite after one devises a treatment that gives them powers to protect their city.
- In a world terrorized by super-villains, one woman has developed the process to give superpowers to regular people. But when scientist Emily Stanton accidentally imbues her estranged best-friend with incredible abilities, the two women must become the first superhero team. Now, it is up to Thunder Force to battle the super-powered Miscreants and save Chicago from the clutches of The King.—Macroplanet
- In March 1983, Earth was subjected to cosmic rays that gave sociopaths superpowers, resulting in a rise of super-villains known as Miscreants. With no one able to stop the Miscreants, normal people are usually left living in fear of being attacked by them. After a Miscreant kills her geneticist parents on their way home from work, Emily Stanton (Octavia Spencer) becomes determined to find a way to stop Miscreants.
By 1985, Emily has sacrificed much of her social life in favor of researching possible methods of fighting back against Miscreants. While this results in her being bullied, Lydia Berman (Melissa McCarthy) stands up for her and becomes her best and only friend. Lydia is dumb as a rock, but loyal to Emily. Lydia supports Emily's dream of giving superpowers to normal people, though she tries to make sure that Emily doesn't overwork herself. When Lydia convinces Emily to take a half-hour nap from studying in 1993, she accidentally causes Emily to oversleep and wake up late for an AP exam, straining their relationship and causing them to drift apart.
In 2024, Emily and Lydia have gone their separate ways, with Emily becoming a successful scientist and researcher for her own company and Lydia becoming a longshoreman. Lydia eats her meals at a cafe run by Frank (Kevin Dunn). Frank and Lydia worry that the miscreants are winning the war and wonder what Emily has been up to. Lydia tries to reconnect with Emily when their high school reunion comes around and invites her to come. When she fails to show up on the night of the reunion, Lydia concludes that Emily is still uncomfortable attending parties by herself and goes to pick her up. Emily tells her that while she would have liked to go to the reunion, she had forgotten when the reunion was and had a project she had to work on that night, which Emily wants to show to Lydia. Unfortunately, Lydia accidentally injects herself with a serum Emily had been working on. Lydia spilled her beer on Emily and when she went out to change clothes, Lydia activated the auto inject mechanism in Emily's lab that pushed the serum in her. The serum Emily injected was for super strength. Allie (Melissa Leo) is ex-CIA and helped Emily set up the whole lab.
Having been injected with the serum, Lydia learns from Emily that the serum was designed to give a normal person superhuman strength and that she would have to undergo special training and treatment so the serum doesn't kill her (once the process is started, it has to be completed else the body will explode in a couple of days). Emily also joins Lydia in the treatment, although a less painful one since Emily took the serum in a pill form to take the other superpower concocted, invisibility. During the thirty-three-day treatment and training, Lydia and Emily grow closer. Lydia can only eat raw meat. Lydia discovers that in the years since their high school graduation, Emily had a daughter, Tracy (Taylor Mosby), with one of the researchers, who could not handle the responsibility and left them. Lydia plays online video games and bonds with Tracy, but Emily tells Tracy not to goof off.
Once they finish their training and treatment, Emily (Bingo) and Lydia (The Hammer) foil a liquor store robbery run by a Miscreant with crab arms known as the Crab (Jason Bateman), who falls in love with an equally smitten Lydia, much to Emily's concern. The girls use a purple Lambo as their ride, a car that they are too fat to get into. Emily and Lydia, known as the superhero team Thunder Force, are praised for their heroics. This brings Thunder Force to the attention of mayoral candidate William "The King" Stevens (Bobby Cannavale), whose campaign is built on the idea that only he can end the Miscreants' crimes. The King has attacked by a Miscreant called Laser, many times during the campaign, bolstering his credentials.
Secretly the King has Crab and Laser on his payroll. The King is also a miscreant himself. With the help of Laser (Pom Klementieff), a Miscreant who can generate and control whip-like energy beams, the King tries to get Thunder Force to work for him, leaving Chicago at the mercy of the Miscreants unless he wins the mayoral election. Thunder Force continues to fight crime with their superpowers and support the rival mayoral candidate Rachel Gonzales (Melissa Ponzio), thereby causing the King to lose the election. The King then sends Laser to attack Thunder Force when they're at a diner. When she tries to get away, Lydia throws a bus at her despite Emily's protests. Though nobody was hurt, Emily decides that Lydia's impulsiveness is more problematic than beneficial, once again straining their friendship.
In an effort to make amends, Lydia goes on a date with the Crab to get some useful information. Along with how the Crab is a misunderstood person who had to turn to a life of crime, Lydia learns that the King is planning on blowing up everyone who did not vote for him in the election, along with the new mayor, at a party he's hosting under the guise of a celebration of the new mayor. She tells Emily of what she learned and makes amends with her.
After fighting off Laser one last time (Allie had secretly made a deal with the King and told them about the Thunder Force's plan to infiltrate the building and steal the bomb. King sent Laser to fight them off), Thunder Force go to stop the King from bombing the building. The King figures out that the Crab told Lydia about his plans, but doesn't fire him. When they manage to find the bomb, the King decides to fight Thunder Force himself, revealing himself to be a Miscreant with superhuman strength, though significantly stronger than Lydia. Before the King can kill Lydia, the crab double crosses him and gets his claws broken off. Tracy also joins the fight, having injected herself with her mother's serum, giving her the ability to run at superhuman speed. Though they manage to take the King down, Thunder Force realizes that the bomb will go off before they can disarm it.
With no guarantee that the bomb would be stable enough to not go off while Tracy carries the bomb to somewhere safe, Lydia decides to sacrifice herself, knowing that she can at least reduce the impact of the explosion. She jumps out the building with the bomb and dives into the Chicago River, seemingly dying in the explosion. However, the paramedics manage to find her body and resuscitate her. Thunder Force, now with a stronger friendship between Emily and Lydia, are offered by the mayor the assistance of the city's resources, which they accept.
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