After an epic rooftop showdown with the Foot Clan, the Turtles find themselves without a stable home. They resort to living off pizza deliveries from "Roy's" Pizza while temporarily staying at April O'Neil's new apartment with their wise mentor, Master Splinter. During a news segment that April presents covering the city's cleanup efforts led by TGRI, Splinter notices the familiar initials tied to the canister of mutagen that transformed them into their mutant forms.
Meanwhile, the menacing Shredder is back on the scene, reestablishing his command over the Foot Clan and thirsting for vengeance against Splinter and his young protégés. Recognizing the potential of the ooze to create mutants, he schemes to secure samples and the expertise of scientists. His nefarious plan includes the kidnapping of Professor David Perry from TGRI, coercing him into helping produce two fierce mutants to serve as his new apprentices: Tokka, a snapping turtle, and Rahzar, a wolf.
When the Turtles are discovered by Keno, the eager pizza delivery boy, within April's apartment, they share their background story. Keno informs them about the Foot Clan's renewed efforts to enlist individuals with combat skills. Intrigued by the idea of infiltrating the Foot, Keno aims to join, but Splinter objects, fearing for his safety. Unwilling to let danger brew in April’s home, Rafael chooses to team up with Keno, while his brothers embark on an expedition to a forgotten Subway Station beneath the city.
In a twist of fate, Professor Perry enhances the mutagen, ensuring that Tokka and Rahzar will possess raw strength without the boon of intelligence. Shredder, persuaded by the professor to spare the mutants for their might, inadvertently creates a dynamic where they view him as a maternal figure.
While infiltrating the Foot, Rafael uncovers that the Shredder has indeed survived, but he finds himself captured and used as bait. Keno alerts the others, prompting a daring rescue mission at the Foot's junkyard stronghold. They fall into a well-laid trap, but Master Splinter intervenes to assist them in battling the Foot Clan and their monstrous recruits, aiming to rescue Professor Perry. Safely back in their Subway lair, Perry divulges all he knows to his new allies.
To counteract the impending threat, Donatello and Perry start concocting an anti-mutagen. Just then, April alerts them to Shredder’s diabolical plot to unleash Tokka and Rahzar upon Central Park unless the Turtles face him in a death match at a nearby construction site. Armed with anti-mutagen doughnuts, the Turtles bravely confront the transformed creatures. The fight escalates to a vibrant nightclub where they unexpectedly interrupt a performance by Vanilla Ice, giving rise to the catchy tune "Ninja Rap."
As the showdown resumes, the doughnuts prove effective, allowing the Turtles to face Shredder himself, who reveals his sinister ambitions to create even more mutants. In a dramatic turn of events, Shredder exposes himself to the ooze, mutating into the terrifying Super Shredder, but in his attempt to destroy the Turtles, he ultimately meets his own demise.
