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.
Baron Boris von Frankenstein (voiced by Boris Karloff) achieves his ultimate ambition, the secret of total destruction. Having perfected and tested the formula, he sends out messenger bats to summon all monsters to the Isle of Evil in the Caribbean Sea. The Baron intends to inform them of his discovery and also to reveal his imminent retirement as head of the "Worldwide Organization of Monsters". Besides Frankenstein's Monster (referred to as "Fang") and the Monster's more intelligent mate (voiced by Phyllis Diller) who live in the island castle with Boris, the invites also include Count Dracula, the Mummy, Quasimodo (referred to as "The Hunchback of Notre Dame"), the Werewolf, The Invisible Man, Dr. Jekyll and Mr. Hyde, and the Creature from the Black Lagoon (referred to as the "Creature").
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.
During the late 1880s, Dr Frankenstein’s evil granddaughter Maria has moved to the American West with her brother Rudolph, in order to use the prairie lightning storms in her experiments on immigrant children snatched from a dying town. Maria is very much in charge, killing the children and replacing their brains with artificial ones, intending to revive them as her slaves. Rudolph however, is reluctant to help his sister, but is too afraid of her to do otherwise. After a number of failures (owing to Rudolph secretly poisoning the victims as soon as his sister revives them), they are finding it increasingly difficult to hide the trail of bodies. Down the road, Mañuel Lopez and his wife Nina decide to leave town with their daughter Juanita because of the frequent disappearances, the latest of which is that of their son.
Herman Munster (Fred Gwynne) and his wife, Lily (Yvonne De Carlo) learn from Cavanaugh Munster's will that they have inherited an English manor known as Munster Hall in Shroudshire, England, and that Herman has inherited the designation Lord Munster. The family boards the SS United States to England. Herman gets seasick, Marilyn (Debbie Watson) encounters Roger Moresby (Robert Pine), and Grandpa (Al Lewis) gets turned into a wolf upon accidentally consuming a wolf pill. Grandpa is sneaked through customs.
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.
All of the women on the planet Mars have died in an atomic war, except for Martian Princess Marcuzan (Marilyn Hanold). Marcuzan and her right-hand man, Dr. Nadir (Lou Cutell), decide they will travel to Earth and steal all of the women on the planet in order to continue the Martian race. The Martians shoot down a space capsule manned by the android Colonel Frank Saunders (Robert Reilly), causing it to crash in Puerto Rico. Frank's electronic brain and the left half of his face are damaged after encountering a trigger-happy Martian and his ray gun. Frank, now "Frankenstein", described by his creator as an "astro-robot without a control system" proceeds to terrorize the island. A subplot involves the martians abducting bikini clad women.
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.
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.
Mexican funnyman, El Clavillazo (Antonio Espino), is in love with a seamstress named Beatriz (Evangelina Elizondo), and also hangs out with a variety of odd characters, including a newsboy and a mental patient. Meanwhile, at the nearby castle, a mad scientist named “Dr Sputnik” and his scarred, hunchbacked assistant are busy making monsters. The doctor poses as a kindly blind man in town and uses hypnosis to lure Beatriz to his castle, brainwashing her into believing that she is his own love named “Galatea”. El Clavillazo, with an assist from his friends, blunders his way into the castle, where he spends most of his time being chased around by various monsters. There is the butler, who looks like the Frankenstein Monster. The rest of the monsters include a werewolf, a mummy, a vampire (clearly modeled after Count Dracula) and a gill-man (clearly patterned after "Creature from the Black Lagoon"). There is also another, unidentified monster being kept in a cell (why it is not allowed to run free with the rest is not known), which is referred to as a “gorilla” in some reviews, although it appears to be more of a humanoid ape-like creature, perhaps based on Dr. Jekyll and Mr. Hyde. In the end, El Clavillazo manages to defeat the monsters, mostly by luck, and rescue the girl. A chemical in Sputnik’s lab devolves the gill-man into a big fish, the werewolf is choked out by the monster in the cell (perhaps that is why he was kept behind bars), Frankenstein accidentally electrocutes himself by grabbing a power cable in the lab and turns into cogs and clock-parts, the mummy falls into a pit of alligators and is devoured, and the vampire vanishes when the sun rises. Dr Sputnik has the usual falling out that all mad scientists seem to eventually have with their deformed assistants (usually due to the scientist mistreating his assistant, or the assistant developing a crush on a girl the scientist has designs on, or sometimes a combination of both), resulting in his being shot after he stabs the scarred hunchback. Clavillazo and Beatriz are trapped in a room and about to be crushed by the walls moving together when they are rescued in the nick of time by the rest of the gang, and they all live happily ever after.
Boris Karloff plays the role of Baron Victor von Frankenstein, who suffered torture and disfigurement at the hands of the Nazis as punishment for not cooperating with them during World War II. Horribly disfigured, he nevertheless continues his work as a scientist. Needing funds to support his experiments, the Baron allows a television crew to shoot a made-for-television horror film about his monster-making family at his castle in Germany.
The grandson of Victor Frankenstein, Oliver (Donald Murphy), is hiding away as a laboratory assistant for the gentle Prof. Morton (Felix Locher). While Dr. Morton pursues a pet project, Dr. Frankenstein secretly works his own experiments on his benefactor's niece, Trudy Morton (Sandra Knight). Although these experiments temporarily disfigure Trudy's face and cause her to wander aimlessly at night, they are only a build-up to Oliver's greater goal of recreating life. With the aid of one of his father's former assistants, Oliver constructs a female monster from the body parts of various murdered people and begins to deal a horrible fate upon any who dare stand in the way of his desires.
Pete Dumond, Chief Make-up Artist for 25 years at American International Studios, is fired after the studio is purchased by NBN Associates. The new management from the East, Jeffrey Clayton and John Nixon, plan to make musicals and comedies -- instead of the horror pictures for which Pete has created his remarkable monster make-ups and made the studio famous. In retaliaton, Pete vows to use the very monsters these men have rejected to destroy them. By mixing a numbing ingredient into his foundation cream and persuading the young actors that their careers are through unless they place themselves in his power, he hypnotizes both Larry Drake and Tony Mantell (who are playing the characters Teenage Werewolf and Teenage Frankenstein, respectively, in the picture Werewolf Meets Frankenstein,currently shooting on the lot).
Professor Frankenstein (Whit Bissell), a guest lecturer from England, talks Dr. Karlton (Robert Burton) into becoming an unwilling accomplice in his secret plan to actually assemble a human being from the parts of different cadavers. After recovering a body from a catastrophic automobile wreck, Professor Frankenstein takes the body to his laboratory-morgue, where in various drawers he keeps spare parts of human beings. The Professor also enlists the aid of Margaret (Phyllis Coates), as his secretary, to keep all callers away from the laboratory.