Wheelchair-bound mad scientist J. Carrol Naish as Dr. Duryea, the last descendant of the original Frankenstein, operates out of a hidden laboratory tucked behind the Creature Emporium, a spooky throwback to the old sideshow days on the Venice boardwalk. With his mute, simple-minded assistant Lon Chaney Jr. as Groton, Duryea conducts horrific experiments on young women to perfect a blood serum. The plan is twofold: the serum could heal his paralyzed legs and, somehow, cure Groton himself. A dwarf named Angelo Rossitto as Grazbo, the ticket taker at the Emporium, helps them traffic their grisly crimes as they push toward their darker aims.
Count Dracula, Zandor Vorkov, arrives with a chilling bargain: he will aid in reviving Frankenstein’s monster—now exhumed from a nearby cemetery—if Duryea lends him the serum, which Dracula hopes will grant him a daylight walk and an apparent invincibility. The duo succeeds in bringing the Monster, now portrayed by John Bloom, back to life to exact revenge on Dr. Beaumont, the scientist who once discredited and crippled Duryea in a laboratory fire. The renewed threat deepens when Judith Fontaine, a Las Vegas showgirl, arrives in search of her missing sister Joanie, who was last seen in the company of Strange, an aging hippie leader played by Greydon Clark. After a failed plea for help from Sgt. Martin, portrayed by Jim Davis, Judith follows clues that lead her to the Creature Emporium, where she, Mike Howard, Samantha, and Strange try to locate Joanie. Duryea denies knowledge of Joanie, and as more girls vanish, the suspense tightens.
The Monster kills two police officers while trying to abduct another victim, while Groton heads to the beach with an axe, killing Rico and his gang and dragging Samantha into Duryea’s laboratory through a hidden trap door. Judith and Mike—who have grown close—discover the trap door and the hidden lab, where Duryea reveals his chilling theory: the fear felt by the dying girls creates a special enzyme in their blood that is the key ingredient for the serum. He hints that Judith’s fear at witnessing Mike’s death could finalize the serum, a revelation that raises the stakes for everyone involved.
Duryea dispatches Groton and Grazbo after the couple, and tragedy strikes Grazbo when he plummets onto an axe that he had dropped earlier. The authorities arrive as Sgt. Martin and Strange lead the pursuit, and Martin shoots Groton from a rooftop, sending him to his death. In a climactic turn, Duryea slips from his wheelchair into a guillotine display and is beheaded, ending his twisted ambitions.
The occult drama escalates as Dracula hypnotizes Judith and binds her in a church where his coffin rests. He confronts Mike, who retaliates by burning the Monster’s face with a lit car flare, briefly turning the Monster against Dracula. Mike frees Judith, and the two flee, but Dracula retaliates with a fiery ring that blazes Mike to ashes. Judith awakens bound in the church, facing Dracula’s plan to transform her into his vampire bride. The Monster, who has fallen for Judith, intervenes by wrenching Dracula’s ring away and compelling Dracula into the surrounding forest. Dracula fights back, ripping off the Monster’s arms and head, but the sun’s rays catch him and he disintegrates into dust. Judith, shaken, finds Dracula’s ashes and pockets the ring, only to drop it and flee, haunted by the night’s horrific memories.