Since ancient times, philosophers have taught that a power outside of our control determines the course of our lives. Zoe, the heroine of this story, rejects this premise even though she spent her early childhood in abusive child care facilities and later grieved the deaths of cherished family members.

Zoe is the story of the life of Zoe (nee Genevieve) Stamos Angelos, a first-generation American woman of Greek-Irish heritage. The main setting is Chicago, Illinois, in the years 1906-2000. Throughout the novel, the author weaves a rich tapestry of ethnic and historical events including the great plague of 1918 and World War II.

Spanning Zoe's life from age seven to ninety, the story explores the complexity of father-daughter relationships, overcoming grief, a woman's struggles to succeed against all odds, and the choices women of different generations make when defying convention in order to find love.