Sixteen-year-old Nanako Misonoo expects a bright future when she enrolls at the prestigious all-girls Seiran Academy. Instead, the unlucky teen is pulled into a tangle of deceit, misery, and envy. To make matters worse, she is selected as the newest member of the Sorority, an elite group that the entire school admires. Lacking the grace, wealth, or talent of her fellow inductees, Nanako quickly becomes a target of jealousy among her classmates—especially the fierce Aya Misaki.
To cope with her increasingly difficult school life, Nanako reflects on her past through letters addressed to her former teacher, Takehiko Henmi, whom she endearingly calls "onii-sama" (big brother). She also finds solace with her four closest friends: childhood friend Tomoko Arikura, sociable yet erratic Mariko Shinobu, troubled musician Rei Asaka, and athletic tomboy Kaoru Orihara.
An impassioned drama centered on the hardships of bullying, Oniisama e... follows a young girl's harsh experience at her new school as she endures cruel rumors, heartless classmates, and countless social trials.