Killer Is Dead follows Mondo Zap, an executioner employed by the Bryan Execution Firm, through 12 episodes set around the world. He carries a katana as his primary weapon, carrying out contracts against cyborgs and assassins in a future setting rendered with cel-shaded visuals.
Each mission begins with an objective briefing displayed against a world map. Animated sequences advance the story between fights, and completing a main mission usually unlocks several side missions.