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.

Stefan invites his daughter, Jennifer, to travel to Romania for the funeral of his mother. His mystic girlfriend Liz travels with them to the cursed village of Pelosoara, where they are welcomed by Stefan's brother Vladimir, and Jennifer finds the locals are very peculiar people. Jennifer learns that she is the only woman from the bloodline of her father. At the funeral a stranger approaches and asks Jennifer to meet him in the square in one hour. When Jennifer arrives at the meeting place, she sees a creature devouring the man she was there to meet and is saved by Thomas. The man tells her that he is the last druid on Earth, protecting the world against the evil ancients. They were defeated by the druids in the past and banished to the spiritual world. That night, there was to be a reclamation ceremony where the evil queen possesses a vessel to open a vortex between the spiritual and the real world to bring the ancients back to Earth...

When Connor Macleod sees his old friend Rachel die in an explosion, he's had it with his immortal life and the endless pain it brings him and those he loves. He locks himself inside the Sanctuary, a Watcher-organized retreat stationed on holy ground, where immortals who are tired of the game can go to forever escape it, as well as to ensure that The Prize never falls into the wrong hands. But when an old enemy, Jacob Kell, and his posse of assassins attack the Sanctuary and kill everyone there but Connor, he is forced out into the open and into battle. Kell and Connor were friends once, and knew each other back when Connor was cast from Glenfinnan; he returned when news came that his mother was to be burned at the stake, and in the attempt to free her, Kell was killed by none other than Connor himself, and became an immortal, bitter with hate, and devoted to making Connor's life a living hell...

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.