Duke Nukem's homecoming takes a deadly turn when his spacecraft is ambushed over Los Angeles, forcing him to bail out into a city already overrun by extraterrestrial invaders. The aliens have transformed the local law enforcement into twisted mutants, leaving Duke as humanity's unlikely last line of defense. Abandoning any hope of the leisure time he'd been counting on, the hardened action hero embarks on a brutal campaign through the ravaged urban landscape and surrounding areas, determined to dismantle the alien occupation before the threat spreads beyond containment.