Shinzo is based in the future. Humanity has been exterminated by a genetic race they created to fight a deadly DNA virus that was wiping out the human race. One of the scientist had placed his young daughter in a cryogenic sleep within a multi-purpose vehicle called Hakuba, hoping that she would awaken 50 years later and find surviving humans, so that she could establish peace between them and the genetic beings, the Enterrans. The girl, Yakumo received special powers at the impact of a meteorite, the impact after which the Enterrans went evil. When she awakens 500 years later sue to a computer error, she goes on a journey and meets three Enterrans: Mushra, Sago, and Kutal, who decide to join her. Together, they seek a location called "Shinzo" where the last hope to restore humanity is said to be located somewhere west, while discovering the secrets of the past. In the unlikely event of powerful enemies, Mushra, Sago, and Kutal can use the power of their gems and form Mushrambo.

In the alternate timeline in Season 2 where Humans and Enterrans are living in peace after Yakumo found Shinzo resulting that there was no Human/Enterran war that wiped out the Human Race. However, the threat of Lanancuras and the Kadrians are at large. Mushra, Sago, and Kutal are joined by Binka in order to reform Mushrambo and find Yakumo.