Genesis Rising: The Universal Crusade takes place in the very distant future, three thousand years after what humans believe was the arrival of "the savior". The human race has conquered most of the Universe. They consider themselves a divine race, and think of all aliens as inferior; those that do not obey are punished or destroyed. The dominion of the human race was insured by organids - genetically designed organic machines, easily adaptable to any enemy strategy.

Only one part of the Universe remains unconquered. It is the galaxy where the Universal Heart, an enigmatic entity that spawned all life and matter into the universe, is hidden. At least, that's what the humans believe...

The player will take on a role of captain Iconah, a battle-hardened fleet commander and a brilliant genetic designer, sent on a quest to explore and conquer the Universal Heart.