Sana is a cheerful high school girl who always puts on a brave face, but her heart aches over a secret she can never reveal. Her greatest wish is for her sickly younger brother, Shun, to get well, which is where the title Genki de Ite ne (Hope You Stay Well) originates. Living under the same roof is Takuya, a boy her age who was taken in by her family after his own parents passed away. Though Sana has been in love with Takuya for years, she believes she is merely his family and cannot confess.

The central conflict emerges when Sana’s beautiful and accomplished older sister, Akane, returns home and announces her engagement to Takuya. To protect the peace of her family, particularly the health of her little brother, Sana swallows her feelings and decides to support their relationship. The story follows the intense emotional strain of Sana being forced to act as the cheerful matchmaker for the boy she loves and her sister, leading to a painful love triangle set within the intimacy of a single household.

The setting is a contemporary Japanese family home and the surrounding city, balancing slice-of-life school scenes with the melodrama of domestic life. The notable narrative arcs include the "Engagement Announcement," where Sana learns of the shocking arrangement and resolves to hide her tears; the "Household Peace" arc, which focuses on her daily efforts to maintain a smile for Shun while dying inside; and the "Confession Unheard," where Sana nearly reveals her truth to Takuya but stops herself for her sister’s sake. The plot deepens when Akane reveals she is aware of Sana's crush, changing the dynamic from simple sacrifice to a complex power struggle between the two sisters over Takuya’s future.