The first season centered around Eva Brighi, a teenage girl who struggles to trust her boyfriend, Giovanni. Eva eventually finds new friends in Eleonora, Federica, Sana, and Silvia, and focuses on herself for a change.

Season 2 broke from the traditional SKAM order of central characters by centering on Martino Rametta, a closeted gay teenager who quickly finds himself falling in love with Niccolò. Leaning on his friends Giovanni, Luca, and Elia, Martino begins to embrace who he truly is

Season 3 focused on Eleonora Sava. She lives with her older brother, completely independent from their parents, and prides herself on being wise beyond her years. However, her confidence threatens to come crashing down when she has to face her romantic feelings for Edoardo, a popular boy at school.

Season 4 focused on Sana Allagui, a Muslim-Italian girl. She begins to struggle to balance her faith and her friendships, as she begins to develop feelings for her brother's best friend, Malik.

Season 5 is the first to move past the original SKAM storylines, centering around Elia Santini. He struggles with toxic masculinity and sexual intimacy, as well as being forced to repeat his senior year of high school without his friends. Throughout the season, he finds himself drawn to classmate Viola.

Season 6 will be the first to focus on a SKAM Italia character without a counterpart from the original Norwegian series, with Asia Giovannelli as the central character. Charismatic, strong, and determined, Asia and her friend group, "The Rebels," will face challenges to their decisive morals and ideals by the arrival of new students, especially Giulio.