During a championship baseball match, the three brothers hear that their grandfather in Japan is in trouble, and head out to help him, conceding the match. When they arrive in Japan, they must use all their powers to defend him against his ancient enemy, who has returned to exact revenge.

In 1985 (the early years of the AIDS epidemic), Karen O'Neil, after a five-year absence and haunted by the recent death of her boxer fiancé, returns to her Colorado hometown to reunite with her family who are leaders within their church and operators of a successful martial arts business. After an ostracized gay teenager named McClain Evans is severely beaten, his mother asks Karen to take him as her secret pupil and teach him the martial way. When the secret gets out that she's his teacher, events unfold that effect her and her family.

In Bellwood, a mysterious figure teleports into town, and immediately starts destroying things. Ben Tennyson, in the form of Heatblast, confronts him. After a short battle, Ben seemingly obliterates the villain. Max Tennyson identifies him as Eon, an alien the Plumbers captured almost two centuries ago. When he arrived, he was half dead and brought a device with him called the Hands of Armageddon, which would open a time rift to the alien's home dimension and unleash his race upon Earth if activated. They travel to the containment facility where Eon is supposed to be kept, only to find it empty and his guardian aged to near-death.

Charlie and Dan have been best friends and business partners for thirty years; their Manhattan public relations firm is on the verge of a huge business deal with a Japanese company. With two weeks to sew up the contract, Dan gets a surprise: a woman he married on a drunken impulse nearly nine years before (annulled the next day) shows up to tell him he's the father of her twins, now seven, and she'll be in jail for 14 days for a political protest. Dan volunteers to keep the tykes, although he's up tight and clueless. With Charlie's help is there any way they can be dad and uncle, meet the kids' expectations, and still land the account?

Melvin Smiley, a successful young hitman, is living a normal all-day life for his jewish fiancé Pam, but kills for money in Paris' organization. In addition, he has a relationship with a beauty from the neighbourhood and gets bothered by a pimply video store guy, because he did not return "King Kong Lives" for two weeks. He and his three teammates Cisco, Crunch and Vince one day decide to kidnap the daughter of super-rich businessman Jiro Nishi - off the record. What they do not know, is that Jiro just went completely bankrupt due to a successless movie production, and, even worse, that his daughter Keiko is the god-daughter of Paris, the boss of the kidnappers. He and his men are now searching for the kidnappers in order to grind them up properly. Meanwhile, handcuffed Keiko falls in love with killer Melvin while both preparing a kosher meal in order to satisfy Pam's visiting parents, who are out of the house with Pam - with a body in the trunk.

The four turtles travel back in time to the days of the legendary and deadly samurai in ancient Japan, where they train to perfect the art of becoming one. The turtles also assist a small village in an uprising.