In an alternate, apocalyptic future that takes place fifty years later, all humans and most of the mutant population have been wiped out, due to an extremely powerful mutant explosion that had mysteriously occurred through unknown means. Only a weathered Raphael, who has most of his childhood memories lost to him, and Donatello (whose consciousness has been transferred into Metalhead) have been traveling throughout the Impossible Wasteland trying to save alive while being pursued by the Verminator and his bikers. Befriending a female meerkat warrior named Mira, the last of her tribe, who harbors the secret to "Paradise" and that she must find a wise turtle called "the Holy Chalupa".
The turtles emerge from their hidden lair in the sewers for the very first time, ready to confront the wondrous and hostile world of New York City and face enemies more dangerous and pizza more delicious than anything they could have imagined. Along the way, they gain a friend in the fiesty teenage April O'Neil and gain enemies in the form of The Foot, The Shredder, and the alien Kraang.
Funnier and ninja-ier than ever before, the show will explore the camaraderie of four teenage brothers learning to rely on themselves and one another as they unravel the mystery of their existence and grow to become the heroes they are destined to be.