The tension of cross-cultural bonds and the mysterious role of one's heritage are but two of the themes of Amy Tan's 1995 novel. It centers on the relationship between a pair of siblings, Olivia, the Chinese-American narrator, and her half-sister Kwan, a Chinese native, who joins her sister's American family in San Francisco following the death of their father, when they are children.

Kwan, who is eight years older than her sibling, proves to be a spirited and loving, but eccentric presence. Indoctrinated with ancient religious beliefs and practices, Kwan believes herself to be possessed of 'yin eyes' that can see the dead, and spends considerable time and energy in conversing with her deceased relatives and friends. For this reason, she is eventually sent to a mental hospital, not long after her arrival.

The Hundred Secret Senses jumps forward decades, with Olivia now a photographer in her late thirties. The middle-aged Kwan, still deeply devoted to her sister, arranges a journalistic assignment for she and her estranged husband Simon, in an attempt to re-unite them. As the trio travel to Kwan's native village of Changmian, the novel comes to focus on Olivia's discovery of the 'World of Yin,' which she had so long disdained. Kwan tells of her incarnation in the 19th century as the servant of Christian missionaries in her native village and of her close friendship with an American woman very much like Olivia.

As Olivia learns more about the 'World of Yin,' she gradually sheds her contemptuous attitude and embraces what she now sees as the deeper wisdom of the 'shadow world,' a place of limitless, boundless love.