Lady Tan's Circle of Women follows the life of Tan Yunxian, a young woman living in 15th-century China, as she navigates the complexities of family, society, and personal ambition. The story begins with Yunxian's arranged marriage to Yang Maoren, a marriage meant to elevate her family's status. Despite initial challenges adjusting to her new life in the Yang household, Yunxian forms close bonds with her husband's concubines, including Lady Kuo and Meiling. However, tensions arise as Yunxian's desire to practice medicine clashes with societal expectations of women's roles.

As Yunxian secretly continues her medical studies, she faces opposition from Lady Kuo, who believes that women should not engage in such activities. Despite this, Yunxian perseveres and becomes proficient in medicine, earning the respect of those around her. However, her clandestine activities put her at odds with her husband and his family, leading to strained relationships and conflicts within the household.

Yunxian's life takes a dramatic turn when she discovers that she is pregnant. Despite her joy at the prospect of motherhood, she faces complications during childbirth, resulting in the loss of her child and a near-death experience. This traumatic event deepens Yunxian's resolve to pursue her medical career and advocate for women's health.

As Yunxian continues to defy societal norms, she becomes embroiled in a web of secrets and betrayals within the Yang household. She uncovers the truth behind the death of Spinster Aunt, a trusted servant, and confronts her husband's involvement in the conspiracy. This revelation strains Yunxian's relationship with Maoren but strengthens her determination to seek justice for Spinster Aunt and hold those responsible accountable.

Despite the challenges she faces, Yunxian finds solace in her friendships with Meiling, Miss Zhao, and other women who support her endeavors. Together, they navigate the complexities of life in a patriarchal society, offering each other comfort and solidarity in times of need.

As Yunxian's reputation as a skilled physician grows, she is called upon to serve as a doctor to Empress Zhang in Beijing. This opportunity presents Yunxian with new challenges and opportunities for personal and professional growth. However, her time in the capital is fraught with danger and tragedy, as she faces a smallpox outbreak and grapples with the consequences of Meiling's miscarriage.

Despite the hardships she endures, Yunxian remains resilient and determined to fulfill her calling as a healer. She returns to her hometown of Wuxi, where she continues to practice medicine and advocate for women's rights. Along the way, she reconciles with her family and finds peace in her role as a healer and advocate for social change.