April O'Neil, ace reporter for Channel 6, investigates recent break-ins, allegedly by Ninjas, which have resulted in the thefts of numerous technologies. A chance encounter with a gang of thieves soon leads her to a bigger story when she is saved from the criminals by four Ninja trained, mutated Turtles.

Baxter Stockman, a mad scientist, is showing an exterminator his new invention: a rat catching robot called Mousers.

Shredder experiments with the Inter-Dimensional Portal, hoping to contact Krangs' Rock Soldiers and prepare an invasion of Earth, but a group of fun-loving aliens called the Neutrionos, renegades in Krang's dimension, take advantage of the Portal's opening and use it to arrive on Earth.

As Shredder lures Splinter into he Technodrome, this time with the promise that a weapon in his possession can restore the sensei to human form, the Turtles confront a giant-sized Krang, now in a new body, in the heart of New York City.