Two amateurish hunters are attacked by creepy birds in the woods. Meanwhile seven delinquents are camping in the forest with their counselor in a program of reintegration to the society. Suddenly they are attacked by the birds and the counselor dies and one of the youngsters is wounded. The brutal Johnson imposes his leadership by force over the others while they are hunted by the birds. Meanwhile ranger Garrett finds one of the hunters passed out in the forest and takes him to the hospital.

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.