Toon star Roger is worried that his wife Jessica is playing pattycake with someone else, so the studio hires detective Eddie Valiant to snoop on her. But the stakes are quickly raised when Marvin Acme is found dead and Roger is the prime suspect.

While incarcerated for murder, cartoonist Jack Deebs found escape by creating Cool World, a series featuring a voluptuous femme fatale named Holli Would. But the artist becomes a prisoner of his own fantasies when Holli transports Jack into Cool World with a scheme to seduce him and bring herself to life. Hard-boiled detective Frank Harris – the only other human in Cool World – cautions Jack with the law: Noids (humans) don't have sex with doodles (cartoons). However, flesh proves weaker than ink as Holli takes human form in Las Vegas, staring in a trans-universal chase that threatens the destruction of both worlds.