Terror strikes when a swarm of Snakehead fish invade the Louisiana swamp land.

Cancer-terminal tycoon Peter Murdoch's secret Wexel Hall Pharmaceuticals lab has developed a blood orchid extract cure. To examine why it works optimally in snakes, they also bread a super-anaconda strain. But the original pair escapes, leaving a bloody trail of corpses. Murdoch runs, instructing his staff to clean up. They keep failing and being eaten like unsuspecting locals, some alive, even after enlisting ruthless big game hunter Hammett. The fast-growing pregnant monster sheds its skin, thus disabling the only tracking device.

Mercenary John Seeger is one of the best in the business. John and his crew are battling some French soldiers on the French-controlled Galmoral Island in Southern Africa as they're trying to rescue the French Ambassador -- there's a coup going on. John gets angry when some of his soldiers unload their machine guns into the Ambassador and his family, blowing the mission and getting his best friend Radio Jones killed. John goes back to the U.S.A. and goes to the home of Radio's wife Shondra, tells her the news, and then promises her that he'll take care of her and her son Eddie. But shortly after he makes that vow, Shondra and Eddie get kidnapped. They were kidnapped by a CIA faction led by CIA dirty deeds man John Dresham and his boss, CIA Black Ops producer Anthony Chapel, who want to force John into doing a mission for them. Kamal Dasan, the son of prominent gun runner Ahmet Dasan, has been arrested and thrown into the Randveld Prison outside of Cape Town, South Africa, and Chapel ...

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.