A new family arrives at the Cesaronis' home: Sofia with her three children, Nina, Irene, and Ivan. The woman is an old acquaintance, having lived in Garbatella twenty years earlier, and there's a secret between her and Giulio that threatens to upend the Cesaronis' lives.

Giulio doesn't give up and tries to rekindle his relationship with Annibale by offering him a share in the wine shop. Sofia has a secret: she's moved to Rome because she suffers from a serious heart condition and must undergo experimental treatments.

All the Cesaronis rally around Francesco in the hospital after a serious accident. Alice, distraught with guilt, wishes she could be by his side and help him. The Cesaronis must come to terms with another shocking piece of news: Annibale, their fourth brother, is gay. Meanwhile, Sofia goes to a job interview in L'Aquila and discovers that her children aren't exactly what she expected.

Alice and Francesco, both wheelchair-bound, are taken in by the Cesaroni household. The situation isn't great, and tensions between her, him, and Rudi threaten to explode at any moment. Annibale becomes embroiled in the Cesaronis' and Stefania's problems: he must help Cesare, who doesn't trust Augusto and fears he might steal money from the liquor store, and Stefania, who must track down Ezio.

Sofia offers to accompany Nina to Rimini to meet Federico, and once they're alone, she takes advantage of the situation to confess that she spent a night of love with Giulio in her youth, but she doesn't tell her she's his daughter. The innkeeper is hesitant to tell Nina he's her father, but Annibale dissuades him.

Marco returns home and discovers that Francesco and Alice have broken up because of her infidelity. To impress Irene, Mimmo offers to help her with her physics homework, but the plan backfires, and when he has to retrieve the originals from the teachers' room, he's forced to ask Rudi for help. Irene becomes increasingly fascinated by the older Cesaroni.

Giulio is finally about to leave for New York, but Lucia, due to an unexpected event, must join Eva in San Francisco. Once again, fate keeps them apart. Rudi urges Irene to forget about the kiss and realize that Mimmo is in love with her. Meanwhile, Francesco forces Alice to move her things from their house.

Irene begins dating Alessio, the high school bully who spearheads the school occupation. Alice tries everything she can to mend her relationship with Francesco, who, to make her jealous, begins dating Arianna, the beautiful physical therapist. Nina tries everything she can to convince Francesco to step back and get back together with Alice.

Mimmo and Rudi are at odds with each other over Irene. To the adults' surprise, Irene isn't in love with Mimmo, but she's smitten with Rudi. Both Sofia and Giulio are busy coping with their children's adolescent torments. Nina, growing closer to Francesco, realizes that she doesn't actually want to become a doctor and, to the admissions committee's surprise, turns down a chance to earn a perfect 30 with honors.

Nina is increasingly in crisis; Federico's attentions aren't making her happy, but she tries, at all costs, to stay close to Francesco. When, tired of her confusion, Federico tells her he's realized she's fallen in love with Francesco, Nina realizes it's over. Happiness, however, isn't around the corner because Francesco and Alice have decided to get married.

Sofia is awaiting her transplant, and Giulio is torn between preparing for Alice and Francesco's wedding and the constant support his friend provides. Nina and Francesco are growing closer: once again, thanks to his friend, Francesco manages to overcome the psychological block that kept him confined to his wheelchair. Stefania, just as she's about to begin turning her gaze to the male gender again, discovers that the ever-kind Luca is gay.

The day before the transplant has arrived, and to exorcise her fear, Sofia decides to throw a party. All her friends flock there, except Giulio, who has decided to stay as far away from her as possible. Alice realizes Francesco's true feelings and decides not to marry him. Stefania finally gives in to Alfredo, and Annibale begins to grow closer to Luca.