Citrusville, Florida, sheriff Bobby Fillmore intends to stop what he views as a rampage by the Man-Thing through his town, but Dr. Strange uses his magic to turn back the sheriff and his posse. Strange then teleports himself, the Man-Thing and Ellen Brandt, wife of the creature's human identity Ted Sallis, to his Sanctum Sanctorum. There, the Sorcerer Supreme explains to Ellen that she has a destiny to fulfill involving the creature that was her husband. At first, she won't accept this, recalling how, though they had once been deeply in love, she and Ted drifted apart in their marriage. Ted's neglect and anger spurred Ellen to betray him, and the super-soldier formula he was working on, to agents of A. I. M. Ted's attempted escape resulted in his becoming the Man-Thing when he injected the formula into himself, then crashed into the swamp.
Meanwhile, in a Florida motel, the Burke family, who had recently encountered the Man-Thing, settle in for the night, when they are visited by an odd being calling himself Mr. Termineus. Angry and frightened, Jack and Gwyneth Burke confront Termineus, but he hypnotizes them into forgetting his presence. He then kisses their sleeping son, Job, and fades away with Job's teddy bear.
Back in his Sanctum, Dr. Strange continues his explanation of Ellen's quest: when the heroes once thought dead returned from their pocket dimension, the stress of their transition shattered the fabric of the Nexus of All Realities which has its Earthly locus in the Everglades. She and the Man-Thing must retrieve the missing shards and restore the Nexus. Understanding this may be the path to her salvation, she agrees.
As the Man-Thing and Ellen return to the swamp via a mystic portal, Mr Termineus appears to Dr. Strange, who immediately dispatches the grinning intruder.