A brilliant but misguided geneticist, Doctor Mochizuki, dreams of creating the ultimate life form. To achieve this, he conducts an inhuman experiment on his own loyal laboratory assistant, Masaru Aso. The experiment merges Masaru with grasshopper DNA and advanced cybernetics, transforming him into a powerful cyborg warrior known as Kamen Rider ZO. Horrified by what has been done to him, Masaru flees into the mountains, where the trauma of his transformation causes him to fall into a deep, comatose sleep that lasts for two years.

He is finally awakened by a mysterious, telepathic distress call, one that sounds strangely like a familiar melody. The message is a simple but urgent plea: protect Hiroshi Mochizuki, the young son of the doctor who experimented on him. As Masaru emerges from his long slumber, he finds himself in a world where Doctor Mochizuki has vanished without a trace. In his absence, the unfinished Neo Organism experiment has run amok, evolving on its own into a monstrous, intelligent entity. This creature, known as Doras, is a grotesque and powerful Kamen Rider-like monster that seeks to perfect itself by any means necessary. To do so, it needs Doctor Mochizuki to complete its evolution, and it believes the key to luring the doctor out of hiding is his son, Hiroshi.

Masaru, still struggling to understand his new powers and his identity as Kamen Rider ZO, tracks down Hiroshi. The young boy lives with his eccentric inventor grandfather, Seikichi, and clings to a pocket watch given to him by his missing father—the same watch that plays the melody that woke Masaru from his coma. Masaru protects Hiroshi from the initial attacks of Doras, but the monster is relentless. It spawns two horrific servants to hunt the boy: Bat Man, a humanoid bat who can disguise himself as a human, and Spider Woman, a four-armed, spider-like creature capable of creating dimensional portals.

Throughout the story, Masaru forms a hesitant but powerful bond with Hiroshi, acting as a surrogate older brother and protector. He reveals to the boy the terrible truth about his father's actions, a revelation that Hiroshi struggles to accept. Bat Man exploits this conflict, disguising himself as Doctor Mochizuki to lure Hiroshi into a trap. Masaru is caught off guard by a full-power Doras and is brutally defeated and absorbed into the monster's body, merging with the Neo Organism to become an even more powerful, red-colored version of Doras.

Inside the creature, Masaru learns the final, tragic truth. Doctor Mochizuki, consumed by guilt, is a prisoner in his own laboratory, trying to undo his terrible mistake. He was the one who sent the telepathic call to awaken Masaru, hoping he would save his son and stop his creation. In a desperate final battle, the music from Hiroshi’s pocket watch echoes through the laboratory, momentarily disorienting Doras and giving ZO the opening he needs to break free. With the boy’s watch still playing, ZO battles the rampaging Neo Organism. Seeing his chance to atone, Doctor Mochizuki sacrifices his own life to destroy the energy pool that sustains the monster, severely weakening it. Kamen Rider ZO then delivers a final, devastating Rider Kick to destroy Doras for good. As the laboratory self-destructs, ZO carries Hiroshi to safety. After returning the boy to his grandfather, Masaru Asou, his duty fulfilled and his past laid to rest, walks away from the city and into the unknown, leaving behind the legacy of Kamen Rider ZO.