In 1979, a group of college students find a Sumerian Book of the Dead in an old wilderness cabin they've rented for a weekend getaway.

Dr. Peyton Westlake is on the verge of realizing a major breakthrough in synthetic skin when his laboratory is destroyed by gangsters. Having been burned beyond recognition and forever altered by an experimental medical procedure, Westlake becomes known as Darkman, assuming alternate identities in his quest for revenge and a new life with a former love.

In the seedy part of Los Angeles, a man who writes poetry has spent six months without leaving his apartment because of his paranoid delusions involving sadistic doctors, rappers, and spiders. A woman who seems to jinx things by wanting to help is dumped by her boyfriend and finds herself penniless on the streets, and soon runs afoul of a local gang. Due to a telephone glitch, the man calls her at a phone booth trying to dial a "talk line" and invites her to his place. There they must help each other to overcome their respective problems.

A pair of whacked-out cartoon-like exterminator/hitmen kill the owner of a burglar-alarm company, and stalk the partner who hired them, his wife, and a nerd framed for the murder, who tells the story in flashback from the electric chair.