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In an underground facility, five scientists wake from cryosleep with no memory of who they are or how long they've been asleep. They soon make a shocking realization: a killer is hunting them down there, and may even be hiding among them.。城市在恢复平静后，大反派重新召集旧部卷土重来，并勾结外星恶势力朗格试图称霸地球，忍者神龟李奥纳多、拉斐尔、多纳泰罗和米开朗琪罗与女记者艾蓓丽尔·奥尼尔、弗农·芬威克，及面具义警凯西·琼斯并肩作战打击恶徒。在史莱德逃脱拘留后，他与疯狂的科学家巴克斯特斯·托克曼及其两个笨拙的左膀右臂猪面和牛头联合，发布了一个控制世界的恶魔计划。在神龟们与史莱德及其同伙对抗的同时，他们发现自己正面临着一个力量强大且更加邪恶的大反派格朗，神龟们面对的将是宇宙级的强大对手。。