Based off of the 1973 anime, Casshern is about Tetsuya Azuma, son of the famous scientist Kotaro, who dies during the alliance wars, but is later reborn into a robot suit to help fight against a new threat to mankind: the Neo Sapiens. The world they live in has been devastated by fifty years of battle between the Greater Eastern Federation and the Europa Alliances. Finally, the Greater Eastern Federation wins the war, but the outcome of years of battle has taken its toll on the world, as it’s now virtually inhabitable. All the nuclear and chemical battles have poisoned the waters, and have left the remaining survivors with almost no chance for survival.
Tetsuya leaves the luxury of his family riches and enlists in the war against the Europa Alliance. During the fighting, his father Kotaro proposed a theory called 'neo-cell.' The neo-cell theory was intended to rejuvenate the body and regenerate any body parts that have been lost due to war or illness. Professor Kotaro’s theory would save mankind from the diseases that the war has caused, and create a better world to live in. The politicians deny his request for funding for research, in fear that the new theory would threaten their powers. However, the military finds the theory interesting, and secretly, they offer the professor funding for his project.
With his father’s project in the works, Tetsuya is experiencing horrors beyond his imagination as he sees the senseless killing of innocent people. During one skirmish, Tetsuya is killed. His mother is told by the military and collapses in disbelief, while Kotaro tells his friend and the father of Tetsuya’s fianc?e of his son’s death at the lab. Luna, Tetsuya's fianc?e, on the other hand, does not know, while she waits for her father to return from the lab.
Tetsuya’s body is returned and is to be given a military burial ceremony. The ceremony is held in front of the lab where his father works. During the ceremony, lighting strikes the lab and sends a bolt of energy to the neo-cell pool. To the amazement and shock of Kotaro, his test subjects begin to revive. One by one, each subject awakens and begins to escape from the lab, only to be killed again by the military. One of the test subjects lands on top of Tetsuya’s coffin, and sees Tetsuya’s spirit as Tetsuya looks at him in a state of shock. Tetsuya’s mother arrives to see her son’s coffin, only to be abducted by one of the test subjects.
Luna finally sees Tetsuya’s body and cries over the loss of her loved one. Kotaro, learning that his wife has been taken, goes mad and takes the lifeless body of his son and drops him into the neo-cell pool, and Tetsuya is revived. Kotaro informs Luna’s father to watch over Tetsuya. The test subjects make their escape, and one by one, each continues to die. Only four remain, and they discover an abandoned castle in the mountains outside of the city. One of the test subjects, Burai believes that Man needs to be cleansed, and that their objective is to eliminate mankind. He and the remaining three mutants declare themselves as the Neo Sapiens. They create various types of robots to unleash a devastating counter attack on the Greater Eastern Federation.