The Sakuragaoka Ninja Clan was an organization of ninjas that was operating in Kyoto, Japan several years before the events of No One Lives Forever 2: A Spy in H.A.R.M.'s Way.

After her parents had been murdered, Isako found herself alone wandering the streets of Kyoto. Luckily she had been found by an older woman who took her in. The daughter of this older woman was the head of the Sakuragaoka Ninja Clan. Isako was accepted by the clan and trained in the ninja arts.

When Isako had turned the age of 14, she was sent on her first mission for the clan to assassinate a merchant who was kidnapping girls to use as prostitutes in his gambling dens. Unbeknownst to the clan or Isako, the man who paid for the mission had set up a trap to impress his boss, the merchant. Isako was easily captured by the merchant. Before he could put her to death, the merchant's European friend requested that he spare Isako's life so that he might serve him. This European friend was The Director and the head of H.A.R.M. Thus Isako had a life debt to The Director.