In Tromaville, a high school for the very special is held hostage by the infamous Diaper Mafia, leading to an accidental explosion caused by the Toxic Avenger, Tromaville's mutated superhero. The explosion creates a dimensional rift, which propels the Toxic Avenger into an alternate reality known as Amortville while simultaneously bringing his evil doppelganger, Noxious Offender, into Tromaville. As the Toxic Avenger adapts to the grim and morally inverted Amortville, he encounters depraved versions of his friends and must contend with the environment's corruption and danger.

Back in Tromaville, the Noxious Offender assumes the Toxic Avenger's life, causing havoc and spreading chaos with his vile behavior. Meanwhile, the real Toxic Avenger, mistaken for his own vile doppelganger in the twisted world of Amortville, must find a way back to his dimension to prevent further disaster. Tromaville's citizens are oblivious to the swap and struggle to reconcile the sudden violent tendencies of their supposed hero, while the Toxic Avenger's pregnant wife grapples with the sudden change in her husband, unaware of the evil twin's true identity.