"Kiss x Sis" centers around Keita Suminoe, a high school student living with his twin stepsisters, Ako and Riko. The three share a close bond, but their relationship takes a complicated turn as Ako and Riko develop romantic feelings for Keita. Despite being stepsiblings, the twins openly express their affection, often competing for his attention in increasingly bold and provocative ways. Keita, while initially hesitant and embarrassed by their advances, finds himself grappling with his own feelings as the lines between familial and romantic love blur.

The narrative explores the dynamics of their unconventional relationship, with Ako and Riko frequently testing boundaries through playful yet suggestive behavior. Ako, the more reserved and studious of the twins, contrasts with Riko, who is outgoing and mischievous. Their personalities create a balance of tension and humor as they navigate their feelings for Keita. The story also introduces other characters, such as classmates and teachers, who add to the comedic and dramatic elements of the plot.

The series delves into themes of love, desire, and the complexities of family relationships, often blending lighthearted humor with moments of emotional introspection. While the twins' pursuit of Keita drives much of the plot, the story also examines their individual growth and the challenges they face in reconciling their feelings with societal norms. The narrative maintains a balance between comedic escapades and heartfelt moments, creating a mix of entertainment and emotional depth.