The story begins on the final day of school before summer vacation. Then the player chooses a sister who he wants to start with for a close relationship. Therefore, Sister Princess 2 is about spending the player's time with either one sister or all sisters at the same time as they spend their summer together. Especially in Sister Princess 2, the player can spend the summer with all the sisters, not just one, in a special ending where the sisters invite their brother to a summer party where the brother and the sisters would swear to be together forever.

Sister Princess 2 has four endings for each sister. The first two were the non-sibling relation and siblings-together ending and, if the player chooses one sister in the beginning but ends up with another sister, either of the other two endings for the first sister who the player does not choose appear ("non-blood relation" ending and "still brother and sister forever" ending also) but with a different story.