The residents of the village of Frankenstein feel they are under a curse and blame all their troubles on Frankenstein's monster. Rumors circulate about Ygor who is still alive and supposedly trying to revive the monster. The villagers pressure the Mayor into allowing them to destroy Frankenstein's castle. Ygor (Béla Lugosi) attempts to put up some resistance, but the villagers rush the gates and begin to destroy the castle. Ygor, fleeing through the catacombs, finds the monster released from his sulfuric tomb by the explosions. The exposure to the sulfur weakened the monster but also preserved him. Unseen by the villagers, Ygor and the monster flee the castle to the surrounding countryside; there they encounter a powerful thunderstorm. The monster is struck by a bolt of lightning, but instead of being harmed by it, he seems to be rejuvenated. Ygor decides to find Ludwig, the second son of the original Frankenstein, to help the monster.
Years later, Frankenstein, now going by the alias of Dr. Stein, has become a successful physician in Carlsbruck, catering to the wealthy while also attending to the poor in a paupers' hospital. Dr. Hans Kleve, a junior member of the medical council, recognises him and blackmails him into allowing him to become his apprentice.
Baron Victor Frankenstein is staying at a boarding house while a former fellow-scientist resides in a nearby insane asylum, slowly dying through lack of oxygen in the brain.
The film focuses on the exploits of the vengeful Dr. Gustav Niemann (Boris Karloff), who escapes from prison. He is helped by the hunchback Daniel (J. Carrol Naish), for whom he promises to create a new, beautiful body. The two murder Professor Lampini (George Zucco), a traveling showman, and take over his horror exhibit. To exact revenge on Bürgermeister Hussman (Sig Ruman), who had once caused his imprisonment, Niemann revives Count Dracula (John Carradine). Dracula seduces Hussmann's granddaughter-in-law Rita (Anne Gwynne) and kills Hussmann himself, but in a subsequent chase, Niemann disposes of Dracula's coffin, causing the vampire to perish in sunlight.
Count Dracula (John Carradine) greets the castle's owner, Dr. Franz Edelmann (Onslow Stevens). The Count, who introduces himself as "Baron Latos", explains that he has come to Visaria to find a cure for his vampirism. Dr. Edelmann agrees to help. 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, whose juices have the ability to reshape bone. Edelmann explains 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.
Meanwhile a local priest discovers the theft and is morally outraged. The young child of the deceased who witnessed the theft identifies both the body-snatcher and his employer. The priest angrily confronts each in turn, and interrupts Frankenstein's attempt to restore life to the heart, smashing vital equipment in the lab. Forced to leave town because of their experiments, Frankenstein and Hans return to the Baron's hometown of Karlstaad, where they plan to sell valuables from the abandoned Frankenstein chateau to fund new work. Nearing the village, the pair nearly run over a wild haired, deaf-mute young woman, who is being accosted by a couple of thugs. Hans tries to help her, but she flees to the hills. The men find a festival is in progress and are able to pass through the village unquestioned.
The prologue is set in Nazi Germany during the final days of World War II. A Kriegsmarine Officer, flanked by three Commandos, barges into the laboratory of a Dr. Riesendorf with orders to seize the immortal heart of the Frankenstein Monster, on which Riesendorf is busy experimenting. The heart is summarily transported by U-Boat to be passed off to their Japanese allies via the Atlantic. In the Indian Ocean, off the Maldives, the U-Boat meets up with a Japanese Imperial Navy submarine to make the exchange. They are sighted by an Allied Forces scout plane and bombed, but not before the Kriegsmarine pass the heart (contained in a locked chest) to the Japanese, who take it back to Hiroshima for further experimentation. But just as the experiments are about to begin, Hiroshima is bombed by the Allied Forces, and the heart and the experiments vanish in the atomic fireball.
As the film opens, a small boat is seen chugging through stormy seas. A giant octopus appears from the ocean and seems bent on killing the sole crew member on deck. Suddenly, the octopus releases the man and retracts its tentacles from the boat. Relieved, the sailor peers out the porthole to see Gaira, a large green man-like creature, fighting the octopus. After easily defeating it, Gaira turns his attention to the boat and sinks it.
Years later, Hans Werner (Robert Morris) is working as an assistant to Baron Victor Frankenstein (Peter Cushing), helped by Dr Hertz (Thorley Walters) who is in the process of discovering a way of trapping the soul of a recently deceased person. Frankenstein believes he can transfer that soul into another recently deceased body to restore it to life.
A mad scientist (J. Carrol Naish) descended from
the original Dr. Frankenstein takes to murdering young women for experimentation in hopes of reviving his ancestor's creation, with help from his mute assistant Groton (Lon Chaney, Jr.). Dracula (played by Roger Engel under the pseudonym "Zandor Vorkov") comes to the scientist promising to revive Frankenstein's monster in return for a serum which will grant him immortality.
After Baron Henry von Frankenstein creates a bride his monster, he decides to make arrangements for a lavish wedding at the Transylvania Astoria Hotel. Many monsters are invited to the wedding including Count Dracula and his son, Ron Chanley the Werewolf, the Mummy, Dr. Jekyll and Mr. Hyde, the Invisible Man and his family, and the Creature from the Black Lagoon. Once the wedding guests arrive, they terrify guests and staff. Frankenstein's assistant Igor is jealous of the monster and wants the bride for his own. So Igor plots to steal her which doesn't go according to plan when the bride ends up snatched up by a Pterodactyl and lands in the clutches of a giant gorilla named Modzoola.
Victor Frankenstein, a cold, arrogant and womanizing genius, is angry when his father forbids him to continue his anatomy experiments. He ruthlessly murders his father by sabotaging the old man's shotgun, consequently inheriting the title of Baron von Frankenstein and the family fortune. He uses the money to enter medical school in Vienna, but is forced to return home when he impregnates the daughter of the Dean.
Six-year-old Ana is a shy girl who lives in the manor house in an isolated Spanish village on the Castilian plateau with her parents Fernando and Teresa and her older sister, Isabel. The year is 1940, and the civil war has just ended with the Francoist victory over the Republican forces. Her aging father spends most of his time absorbed in tending to and writing about his beehives; her much younger mother is caught up in daydreams about a distant lover, to whom she writes letters. The entire family is only ever seen together in a single shot towards the end of the movie, there is no discussion. Ana's closest companion is Isabel, who loves her but cannot resist playing on her little sister's gullibility. Teresa writes to her past lover while she seems to stare out the window at the old house where Ana will find the republican soldier: "Little but the walls remain of the house you once knew, I often wonder what became of everything we had there." This supposes the house has a history for her, and implies the escaped republican soldier who will run straight to this now empty and crumbling house and hide in it may have been her lover.