The story of Ore no Imouto P-Zoku follows the story of the light novels, continuing from where the story in Ore no Imouto Portable ended.
Each of the story routes featuring the main characters assume that the player reaches the point where in Kyousuke Kousaka has started a romantic relation with one of the main characters, and follows through the story.
New characters were introduced, including Kanako Kurusu's older sister Kanata and Saori Bajeena's older sister Kaori, which both debuted in the light novels as well.