The narrative of Hantsuki revolves around Yuuichi Ezaki and Rika Akiba's developing romance. Both are teenagers, aged seventeen, who are afflicted with health issues - Yuuichi has hepatitis A while Rika is dealing with a weak heart valve. As they recover in their hometown of Ise, Mie prefecture, which is indicated by the "Welcome to Ise" sign displayed after the opening sequence in the first episode of the anime series, the two teenagers form a close bond and eventually fall in love.