Immediately following Metroid Prime 3, it's the height of the Space Pirate War, but the Phazon crisis has finally been resolved. However, that victory came at a cost, leaving Samus Aran as the only surviving bounty hunter of that final mission. Now she must deal with the changing tides of war and the emergence of a mysterious stalker bent on destroying the Galactic Federation itself and anyone else needed to achieve that goal.

But Samus has her own issues to deal with as well, ranging from the after effects of her phazon corruption to taking up the slack of the other three hunters she had been forced to put down. And it would seem the Space Pirates are not the only ones who care to see to her demise...

(Takes place in the Human Series AU five years prior to the start of “Human”)