During World War II, Frankenstein's heart was brought to Japan from Germany and transported to a laboratory in Hiroshima in hopes that the immortal heart could be studied to unlock the secrets it might posses. However, while the heart was under examination, Hiroshima was struck by an atom bomb on August 6, 1945, burning the laboratory to the ground in seconds.

In 1960, 15 years later, a boy is found roaming the streets, eating dogs, rabbits, and anything else the vagrant child can get its hands on. With word of the child spreading, it's not long before doctors Sueko Togami and James Bowen discover the boy for themselves, before the child quickly runs off. Next, reports come in of the vagrant child being cornered in a small cave. The two doctors immediately enter the cave to try and locate the small boy they had seen the night before, and take him back to their clinic for further study. The small child is found cowering in a corner, trying to scare away the onlookers, until Sueko begins to befriend the child and he is taken back with the two doctors. Once at the clinic, the vagrant child begins to grow at an alarming rate, as news of this miraculous discovery continues to spread. Kawai, a man aboard the sub that ferried Frankenstein's heart to Hiroshima in 1945, visits the clinic to see the doctors upon hearing of the remarkable child. Kawai tells the doctors of the incident, and how the heart was transported nearby before the atom bomb hit, leaving room for speculation that perhaps there is a connection.

To follow up Kawai's theory, Dr. Yuzo Kawaji and Dr. Bowen both disembark for Germany to see Dr. Reisendorf, the man who had Frankenstein's heart before it was taken to Japan. Reisendorf explains that if the doctors truly want to find out if the child they have in custody is a descendent of the Frankenstein's monster, then all they have to do is severe one of the child's limbs. If the boy is in fact Frankenstein's monster, Reisendorf assures them that the creature will regenerate its missing limb. The two doctors return to Japan with the information, and Dr. Sueko is mortified by the revelation and entirely opposed to harming the child. Kawaji, however, intends to find the answer by himself, and secretly goes to visit the child at night with the plan of removing one of the boy's limbs. The doctor is interrupted, however, when a group representing TTV barges down to where the child is being confined. The camera crew shines light at the overly large child, now much larger than an average human, as they prepare to film the creature. The vagrant goes berserk in response, smashing out of his confinements and escaping from the clinic. The creature stops off at Sueko's house, to visit the young doctor one last time before it flees from Hiroshima. Shortly after the break out, a severed hand is found moving around the clinic, proving that in fact the monster is Frankenstein.

Following his departure from Hiroshima, Frankenstein ventures to Okayama, where it's discovered that the creature has grown to a height of four people. The monster continues its trek, next visiting Himeji, where the creature devours some of the local live stock before moving on. The monster is next sighted in Byoko, where it openly attacks a pleasure cruise ship, before sinking back into the water. Meanwhile, back at the clinic, it's discovered that Frankenstein's hand has escaped. A short search is conducted, until the shriveled hand is found under a grid, dead from a lack of nutrients.

With word of the pleasure cruise incident spreading, combined with the local disasters caused by the monster Baragon who continues to leave no survivors to report his attacks, the Japanese Self Defense Force begins to mobilize to confront Frankenstein. Appearing in the mountains, trying to capture a large boar, Frankenstein is meant with minimal military resistance, as a few tanks have been dispatched. Avoiding their direct line of sight, the monster quickly flees before the tanks even have a chance to take aim. Meanwhile, Baragon is attacking a nearby village, devouring the small population and flattening the structures. The military arrives too late, and blames Baragon's attack on Frankenstein. Word then spreads that Frankenstein has trapped itself in an abandoned ammunitions cave. The SDF quickly disembarks and confronts the trapped creature. The soldiers in charge quickly open fire on the beast, but their attacks appear to have no effect and Frankenstein quickly flees from the cave.

Kawaji, still insistent on furthering his study, goes after Frankenstein hoping to preserve just a part of his body that can be taken back to the clinic. His plan backfires, however, as the monster Baragon is awakened by the three doctors' presence. Ready to descend on the defenseless physicians, Baragon is instead attacked as Frankenstein rushes to their aid. The two titans clash in an epic battle, which Frankenstein eventually wins as he chokes Baragon to death. The monster is victorious, but has no time to celebrate over the fallen Baragon as a fissure opens, casting both of the monsters down into the depths of the Earth.