After years of being sheltered from the human world, the Turtle brothers set out to win the hearts of New Yorkers and be accepted as normal teenagers through heroic acts. Their new friend April O'Neil helps them take on a mysterious crime syndicate, but they soon get in over their heads when an army of mutants is unleashed upon them.

Josh Futturman, a janitor by day/world-ranked gamer by night, is tasked with preventing the extinction of humanity after mysterious visitors from the future proclaim him the key to defeating the imminent super-race invasion.