The development of Metroid Prime started with an original game Retro Studios was creating for the Nintendo GameCube titled "MetaForce". The game was initially a third-person action-adventure game starring three genetically modified women with different playstyles that made up the titular MetaForce. They consisted of a cyborg named Brynn, a psychic ninja named Miko, and a rifle-wielding assassin. The game took place in a near future world where gene editing had become inexpensive and common. It would have had three 10-hour chapters, each with its own antagonist that acted as an arch-nemesis of the one of the girls. Chapter 1's villain was a Luddite cult leader terrorist who used gene editing to create an army of four-armed mutant foot soldiers. Chapter 2's villain was a Nazi eugenicist who wanted to steal the MetaForce girls' DNA to engineer "a master race of hotties". Chapter 3's villain was a mind-controlling South African who was the mastermind behind all of the preceding events, which were intended to be a distraction from his true plans.

Retro Studios received conflicting feedback from Nintendo of America and co-producer Shigeru Miyamoto. NoA asked them to switch to a first-person perspective, cut any two of the girls, and improve the remaining girl's controls, leaving Brynn as the sole protagonist. Miyamoto then told them that he felt Brynn was too generic of a protagonist and was uncertain about the game being a first-person shooter. From here, the team would switch back to third-person and completely rewrite the game. It now took place in the 1970's and starred an alien protagonist that the United States government had discovered in a crashed UFO. A government team called "MetaForce" then raised it as their own to combat another evil alien race planning to invade and enslave humanity. One day out of nowhere, Miyamoto commented that the game's new alien designs would make for great Space Pirates, and asked the developers if they would prefer to make a Metroid game instead. They agreed, and MetaForce was cancelled in favor of what would become Metroid Prime.