After the events of Sayonara Galaxy Express 999, Tetsuro Hoshino has grown from a boy into a young man. He now works as an assistant at a medical clinic dedicated to helping mechanized people who can no longer maintain themselves following the collapse of the Mechanized Mother Planet. Though celebrated across the galaxy as the hero who liberated humanity from the Mechanized Empire, Tetsuro has sealed away his warrior's gun, hoping for peace on Earth. But his efforts to aid former enemies mark him as a traitor in the eyes of an extremist group. He is ambushed and nearly killed, only to be rescued by the space pirate Queen Emeraldas. She delivers a startling revelation: Maetel has vanished, and she charges Tetsuro with the mission of bringing her back. Reluctantly, he embarks on his third journey aboard the Galaxy Express 999.

As the train departs from the station Destiny, the Metanoid faction—a hostile force that views Tetsuro as the most dangerous being in the universe—triggers a catastrophic event. They artificially induce the Sun to go supernova, obliterating the entire Solar System. This loss of his home world deepens Tetsuro’s resolve. The journey becomes a race against time, with Metanoid assassins and the shadow of a reawakened New Mechanized Empire closing in.

At the heart of this new story lies the bond between Tetsuro and Maetel. While the earlier film adaptations focused on Tetsuro's coming-of-age, this narrative shifts emphasis to their pure and enduring love. Along the way, a host of characters from Leiji Matsumoto’s wider universe appear: Captain Harlock, the indomitable space pirate; Emeraldas, who carries her own secrets; the mysterious Tochiro; and the ever-faithful Conductor. The plot weaves in elements from Matsumoto’s other works, including the legendary battleship Yamato, creating a grand crossover.

The narrative arc unfolds in two major phases. The first covers Tetsuro’s forced departure, the destruction of the Solar System, and his pursuit of Maetel across the galaxy. The second, which resumed after a hiatus, introduces the New Mechanized Empire led by the formidable Darknas. The 999 is captured by the empire’s mobile fortress, and Maetel must confront Darknas directly while Tetsuro faces his old nemesis, the Black Knight Geisel. The final battle is one of both action and emotional reckoning, as the forces of light and dark—shaped by Tetsuro’s sincerity—begin to understand one another and take steps toward a new future. The story concludes with Tetsuro continuing his quest to restore the vanished Solar System, heading toward the final stop called Eternal.