After a scientist is mysteriously killed while assisting a top-secret bioengineering project in the swamps of the American South, government worker Alice Cable arrives at the bogs to serve as his replacement. She immediately notices that one of the team's swamp sensors has malfunctioned, but her guide, Charlie, introduces her to Harry Ritter, the project supervisor.
After her mother's mysterious death, Abigail Arcane (Heather Locklear) travels to the Florida swamps to confront her evil stepfather Anton Arcane (Louis Jourdan), who had been resurrected after his death in the first film. In an attempt to stave off the effects of aging, Dr. Arcane, assisted by Dr. Lana Zurrell (Sarah Douglas (actress)), combines genes from various swamp animals and human beings, creating an army of monsters known as Un-Men. Dr. Arcane tries to use his stepdaughter Abby in his genetic experiments until she is rescued by Swamp Thing (Dick Durock), a scientist previously transformed into a bog creature after a confrontation with the evil doctor.