In 1933, while searching for her vampire father, dhampir Rayne is recruited by the Brimstone Society, a secret society that monitors and combats supernatural threats to humanity. For her first mission, Rayne is deployed to the town of Mortton, Louisiana, to investigate reports of a plague that is transforming local residents into zombie-like mutants. She is accompanied by Mynce, her mentor and fellow dhampir.
In Mortton, Rayne finds the town infested by spider-like monsters called Maraisreq, one of which devours and apparently kills Mynce. After killing the "queen" Maraisreq, Rayne finds a strange glowing rib in its corpse; when she touches it, the rib immediately implants itself into her own torso. Before she can recover from the shock, Rayne is attacked by a man in a Nazi uniform who forcibly removes the rib from her body and leaves her for dead, although she survives.