A recent catastrophe in the player-character's city has killed or turned most of its people into mutants. The player has to "figure out how to deal with" the mutants. The game is set in the near future.
Insomniac Games CEO Ted Price has said that the game's irreverence and stylization reflects the personality of the company. He compared the game's humor to that of Spyro and Ratchet & Clank. The style is driven by the game's story "theme of freedom and self-expression".