Heidi is a resourceful 12-year-old girl living in an apartment in Reno, Nevada, with her mother. She does not know her own birthday or family history, and she possesses an uncanny, unexplained luck with games of chance. Educated at home and eager to understand her origins, she decides to set out on a cross-country journey to discover the truth about her past after finding a mysterious roll of undeveloped film.

Mama is Heidi's mother, a gentle but mentally challenged woman who lives in an insulated world in Reno. She knows only 23 words, including the mysterious word "soof," and struggles with basic caretaking tasks. Despite her cognitive limitations, she enjoys simple routines like making tea and going on walks, communicating her deep affection for Heidi in her own unique ways.

Bernadette, whom Heidi calls Bernie, is the agoraphobic next-door neighbor who serves as a caretaker and teacher for both Heidi and Mama. Unable to leave her apartment since her father's death, she orders supplies via catalogs and creates a safe, insulated world for the three of them. She is practical, fiercely protective, and relies on her vast library to homeschool Heidi.

Thurman Hill is the administrator of Hilltop Home, a facility for challenged adults in Liberty, New York. He is a defensive and guarded man who holds the answers to Heidi's pressing questions about her mother's past but actively tries to conceal them to protect his own interests.

Diane DeMuth is a shadowy figure from Mama's past whose choices heavily influence Heidi's current living situation. She orchestrates agreements that ensure housing and resources for her daughter before disappearing from their lives, leaving behind a trail of unanswered questions.

Alice is a talkative traveler heading to a family reunion in Salt Lake City who becomes Heidi's first companion on the cross-country trip. Her constant chatter about family traditions and shared birthdays inadvertently makes Heidi feel uncomfortable and isolated about her own lack of family history.

Georgia is a kind, perceptive young woman traveling by bus to attend college and study psychology. She acts as a comforting presence for Heidi, teaching her about nonverbal communication and providing a safe, non-judgmental space for Heidi to share the truth about her unusual family situation.

Elliot is a mentally challenged resident of Hilltop Home and the son of the facility's administrator. He frequently repeats the word "soof" to self-soothe and comfort himself, demonstrating a strong, lasting attachment to Heidi's mother from their time together at the home.

Roy is a local sheriff, and his wife Ruby works as a caretaker at Hilltop Home. Together, they form a supportive and grounded unit for Heidi when she arrives in Liberty, providing her with home-cooked meals, shelter, and guidance as she deals with the confusing situation surrounding Mr. Hill.

Zander is a boy who lives in the same apartment building as Heidi and Bernadette. He enjoys making up extravagant stories about himself and his family, trading snacks like Twinkies and Devil Dogs for Heidi's willingness to listen to his tall tales. Despite his tendency to exaggerate, he proves remarkably reliable during emergencies.