The quiet town of Quartz Hill is about to experience the worst night of the town's history. A notorious killer has escaped from death row with one thought on his mind. Revenge.

After the departure of Rube Sofer, a new head reaper named Cameron Kane takes over. He's a slick businessman who couldn't care less about helping the newly dead. Chaos ensues and brings out the worst in Daisy and Mason who begin drinking anew. George and Reggie re-connect for the first time when George reaps a new friend of Reggie's.

Sam Reide has the ability of traveling to the past and works to the police department solving unresolved crimes, witnessing the events with the support of his sister Jenna Reide and reporting the criminal's identity to Detective Dan Glenn. When Elizabeth Brown that is the sister of his former girlfriend Rebecca Brown that was murdered a couple of years ago pays a visit to him, she tells that she has just found Rebecca's journal with evidences that Lonnie Flennons, who was accused for the murder, is innocent. Sam decides to witness the murder of Rebecca and his interference affects the future. He travels to the past other times trying to fix his mistakes, but every time he returns, the future is in worse condition.

Sai, a young artist living in a downtown warehouse delves into an ancient world of blood and lust. An enigmatic foreigner seduces her to try a long forgotten drug making her the prey of a dimensional vampire who needs her new found hunger for blood to cross over from his world to hers.

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.

As retribution a psychopathic stalker known only as The Laugh attacks the now adult girls who picked on his sick childhood tendencies. Tabitha, Shelby and Lisa become the target of a madman with a serious adolescent grudge.

When most of the population of Earth is infected with a virus and transformed into flesh eaters and blood drinking creatures, a group of hunters led by Tao chases the vampire zombies to eliminate them. Six non-infected survivors try to find the exit of an abandoned hospital crowded with the infected creatures, and Tao and his group help them. Meanwhile, the military command is ready to bomb the area and wipe it from the map.