De acordo com o criador do jogo, Tomonobu Itagaki, os jogos no universo Ninja Gaiden (os dois novos jogos e a Trilogia NES anterior) formam uma história contínua e única
VideoGamer.com: We've read that this is the last chapter in the Ninja Gaiden saga. Is there any truth to that?
TI: I really put all my heart and soul into making this the definitive game in the Ninja Gaiden franchise. So I personally don't intend to make any more. This is a game we basically built from the ground up. We threw away everything we had from the first game, improved on what was good, changed what was bad. So it's been a long project, it's been close to three years in the making. We were able to accomplish everything that we wanted to achieve with this franchise.
In story chronology as well, this takes place after the first Ninja Gaiden for Xbox and then after, the story of this game it leads into the old NES ones, so I think we have a nice continuity there.
Obviamente, isso não leva em conta alguma descontinuidade canônica, mas isso pode ser atribuído a erros de produção.