"Saving Francesca" is the story of sixteen-year-old Francesca Spinelli's coming-of-age during a time when her mother, previously the rock of her life, is bedridden with depression. As her family falls apart around her, Francesca falls in love with an unattainable boy, makes new friends, and learns to appreciate what truly makes her unique.

The novel opens with the sorrowful line, "This morning, my mother didn't get out of bed" (Page 1). Francesca Spinelli is used to her mother's ridiculous antics waking her up in the morning, used to her mother's controlling presence in her life, used to her mother's seemingly unattainable expectations for Francesca to live as an individual at all times. Now, her mother is like a ghost, completely bedridden and practically unresponsive to the world around her. Recently, Francesca's mother transferred Francesca from St. Stella Academy to St. Sebastian's - which used to be an all boys' school - for tenth grade. At this new school, there are thirty girls to seven hundred and fifty boys. For many teenage girls, this sounds like a dream come true, but for Francesca, it's a nightmare. She misses her old friends and is forced to hangout with nerdy girls who transferred from her old school with her. As a result, Francesca feels isolated at school and wishes things in her life were different.

One of the major problems in Francesca's life is the fact that girls are treated so differently in school than boys, so some of the ex-Stella girls create a list of demands and nominate Francesca to deliver their request to the house head, a no-nonsense twelfth-year named William Trombol. Even though William is gruff and sometimes rude, Francesca slowly realizes that she's falling in love with Will, and she believes Will might have feelings for her, too. At a party one weekend, Will locks eyes with Francesca from across the room, makes a beeline toward her, and kisses her hard on the mouth. They spend the rest of the party making-out, so Francesca feels blindsided when, the next day, she learns that Will has a girlfriend. Faced with a broken heart and a mother too depressed to get out of bed, Francesca feels as if she's falling apart. Slowly, she begins to bond with her fellow ex-Stella girls and forms friendships stronger than she ever could have imagined. These three girls, Siobhan, Tina, and Justine, never question Francesca's swinging moods: they love her unconditionally, which is more than Francesca can say about her previous best friends, who abandon her in her time of need.

As the novel progresses and Francesca's mother goes from bad to worse, she is forced to lean on her new friends for strength in both her familial and social lives. She learns that being "cool" isn't the most important thing for a teenager - being surrounded by those who love and support you is. As Francesca comes out of her shell, embracing extracurricular activities like dancing and singing in the school musical, she learns to love herself and to surround herself with friends who love her for her she is, not what she represents. The more Francesca heals, the more attractive she becomes to Will Trombol, who soon breaks up with his girlfriend (although he doesn't want to date Francesca right away). Francesca learns that healing is not an overnight experience, for herself or for her mother, but when given the space to truly be themselves, both characters express the strength and determination to survive.