The film opens with a shot of a cliffside castle in Visaria. A mysterious bat circles the area and turns into Count Dracula (John Carradine). He enters the house and greets its owner, Dr. Franz Edelmann (Onslow Stevens). The count explains to the doctor that he has come to Visaria, under the alias "Baron Latos", to find a cure for his vampirism. Dr. Edelmann agrees to help the count and lets him keep his coffin in the castle's cellar. Together with his assistants, Milizia (Martha O'Driscoll) and the hunchbacked Nina (Poni Adams), he has been working on a mysterious plant, the clavaria formosa, with juices that have the ability to reshape bone structure. The count returns that evening, and Edelmann explains to him that he thinks vampirism can be cured by a series of blood transfusions. Dracula agrees to this, and Edelmann uses his own blood for the transfusions.
That night, Lawrence Talbot (Lon Chaney, Jr.) arrives at the castle, demanding to see Dr. Edelmann and seeking a cure for his lycanthropy. Talbot is asked to wait, but knowing that the moon is rising, Talbot has himself incarcerated by the police. A crowd of curious villagers gathers outside the police station, led by the suspicious Steinmuhl (Skelton Knaggs). Inspector Holtz (Lionel Atwill) asks Edelmann to see Talbot, and as the full moon rises, they both witness him transform into the Wolfman. Edelmann and Milizia take pity on the lycanthrope, and have him transferred to his castle the next morning. Edelmann tells him that he believes that Talbot's transformations are not triggered by the moonlight, but by pressure on the brain. He believes he can relieve the pressure, but Talbot must wait for him to gather more mold from his flowers. Talbot cannot stand another night as a beast, so he runs to the cliffs behind the mansion, and throws himself off.
The doctor goes down the cliffs via a harness, and enters the caves below, looking for Talbot, but he has by this point turned into the Wolfman and attacks the doctor. Luckily, he was at the end of his transformation, and he turns back into Talbot. While in the cave, they discover the Frankenstein monster (Glenn Strange), trapped in the mud, still clutching the skeleton of Dr. Niemann. He is alive, but yet again in a catatonic state. They also discover that the damp humidity in the caves, are perfect for growing more of the plants needed for Talbot's operation, and that the caves connect to a large room underneath Edelmann's home. Dr. Edelmann takes the monster back to his lab and considers reviving him, for the sake of science, but decides that it would be too dangerous.
That night, Milizia is playing the piano in the living room, and Dracula appears. The Count tries to seduce her to become a vampire like himself but Milizia brandishes a crucifix before he can bite her. Edelmann interrupts the hypnosis, and explains that he has found strange antibodies in the Count's blood. They decide to have another transfusion the next day. Meanwhile, Nina is following Milizia, who is getting weak because of Dracula's influence. She catches her talking to the Count by a hall mirror and sees that the Count casts no reflection.
Meanwhile, Nina warns Edelmann of the vampire's intentions to make Milizia his undead bride. He prepares for a transfusion that will destroy the vampire and has Dracula come to the lab. During the transfusion, Dracula uses his hypnotic powers to send both Edelmann and Nina to sleep and reverses the flow of the transfusion, sending his own blood into the doctor's veins. When the doctor and his assistant awaken, Dracula is preparing to take Milizia away. They wake up Talbot, and fight Dracula off with a crucifix, who returns to his coffin as the sun is beginning to rise. Edelmann follows him, and drags his opened coffin into a spot of sunlight, and Dracula is destroyed, leaving only his skeleton.
Edelmann on the other hand, starts feeling sick. His blood can't handle Dracula's vampire blood, and he is infected by Dracula's evil. He returns to his room, and watches in horror as his mirror reflection vanishes. He passes out and sees strange visions of himself performing unspeakable acts. When he awakens, his face has changed, now looking as an evil Hyde-like version of himself just like in his vision. He quickly rushes to the lab, to awaken the Frankenstein monster, but Nina interrupts him.
Edelmann finally performs the operation on Talbot. Afterwards, he suffers another transformation into his evil self and brutally tears his garderner, Siegfried's (Ludwig Stossel) throat open. When the townspeople discover the body, they begin chasing Edelmann, believing him to be Talbot. They follow him to the castle and Holtz, followed by Steinmuhl, interrogate Talbot and Edelmann. Steinmuhl is convinced that Edelmann is the murderer, and assembles a mob to execute justice.
The operation on Talbot was a success, but Edelmann again turns into his evil self, and makes a final attempt to revive the Frankenstein monster, who awakens but is very frail. Nina is horrified when she finds her employer, and Edelmann breaks her neck, and tosses her body down the hole leading to the caves. The townspeople arrive, followed by Holtz and Talbot. The police try to attack the Frankenstein monster, who knocks them to the ground, and Edelmann throws Holtz against some lab equipment, electrocuting him. Talbot grabs a gun off of a dead policeman, and shoots Hyde-like version of Edelmann, who falls to the floor, dead. Talbot then attacks the Frankenstein monster, pushing some shelves over him. A fire breaks out, and the townspeople flee the burning castle. The Frankenstein monster is trapped inside as the roof crashes down on him.
- Lon Chaney, Jr. as Lawrence Talbot / The Wolf Man
- Martha O'Driscoll as Milizia Morelle
- John Carradine as Count Dracula
- Onslow Stevens as Dr. Franz Edelmann
- Lionel Atwill as Police Inspector Holtz
- Jane Adams as Nina
- Glenn Strange as Frankenstein's monster
- Ludwig Stossel as Siegfried
- Skelton Knaggs as Steinmuhl
Also appearing in the film is Jane Adams, whose character, Nina, is a hunchback and was thus billed as one of the monsters in the film. In fact, her character is portrayed sympathetically and the use of an attractive actress to play an otherwise misshapen individual is notable for the time.