The novel introduces the concept of "Fukú," a curse believed to plague Oscar's family for generations. Originating in the Dominican Republic during the brutal dictatorship of Rafael Trujillo, the Fukú represents the lingering trauma of political oppression, violence, and exile. It becomes a powerful metaphor for how history, both personal and national, shapes individual destinies and family legacies.

Oscar, a self-proclaimed "Dominican York" and science fiction fanatic, grapples with his dual identity as a Dominican-American. He feels like an outsider in both the Dominican Republic and the United States, struggling to reconcile his family's cultural heritage with his own aspirations. His sister, Lola, rebels against societal expectations of Dominican women, seeking liberation on her own terms.

Despite the shadow of the Fukú, the characters in "The Brief Wondrous Life of Oscar Wao" yearn for love and connection. Oscar, despite numerous romantic failures, remains a hopeless romantic, while Lola navigates tumultuous relationships in search of agency and self-discovery. Their mother, Belicia, carries the scars of a difficult past, but her fierce love for her children fuels her resilience.