一队摄制人员为寻访神秘的希里莎纳部落，正向神秘的亚马逊原始森林迈进。途中他们遇见已在森林里生活多年的“捕蟒专家”，他一直在追捕一条长达40英尺、凶猛而且狡猾的巨蟒。为了借助摄制组的力量，他以带路为借口，把摄制组带进这条巨蟒的领域。就这样，摄制组在毫无准备之下陷入了极度的危险之中……..Picking up immediately where Anaconda 3 left off, herpetologist Amanda Hayes finally learns her employer Murdoch's true colors when he hires a doctor to harvest a fresh supply of blood orchids to experiment with the regenerative nectar on a baby snake in order to seek treatment for his own terminal illness. Amanda is forced to secretly bring together another team of scientists whom face off against a heavily armed squad of Murdoch's men to steal the coveted orchids before the killer Anaconda hunts both parties down.
