One of the central themes in So Far From God revolves around the societal expectations of women. Traditionally, Hispanic women are raised to serve three main figures: their father, husband, and child. These roles can be quite restrictive, especially for contemporary women, and Castillo critiques this portrayal in her novel. The daughters—Esperanza, Fe, Caridad, and La Loca—all strive to be devoted daughters and wives but find themselves failing in these capacities. Esperanza's boyfriend abandons her for someone else, while Fe's spouse drives her to a job that ultimately leads to her demise. Caridad's marriage disintegrates along with all her other relationships, and La Loca's aversion to people makes romance impossible. Even Sofi behaves as a dutiful daughter, foregoing the opportunity for true love. However, Castillo complicates this theme by showing that the alternatives to traditional roles are equally unsuccessful. Esperanza prioritizes her career over family, which leads to her death, and her three sisters all choose paths that diverge from the traditional wife and mother roles, dying without children as well. Castillo implies that women need to recognize themselves as individuals first to achieve true success. Sofi loses everything her culture deems valuable: her husband, her children, and even her home. Only when she has nothing left does Sofi understand that she must live for herself as a woman, not merely as someone's daughter, wife, or mother.

The theme of exploitation is prevalent in twentieth-century American literature, and So Far From God is no exception. In this novel, exploitation impacts women both at home and in the workplace. Esperanza sacrifices her life for her job, as does Fe, but Fe's situation is particularly severe. Her employers at the bank and the factory disregard her humanity. The factory manager exploits Fe's eagerness to perform any task to make a good impression and earn a bonus. She soon realizes the chemicals she handles are deadly, and the company is indifferent. Her death is agonizing and prolonged as cancer ravages her body. Sofi also suffers from emotional and unlawful exploitation. Her husband continuously gambles, ultimately losing their house and property in a card game. Although the judge who wins Domingo's bet knows his actions are illegal—since Domingo neither owned the land nor could the judge legally claim it—he still forces Sofi to pay rent on her own home. She is unable to sue him due to his position as a judge, allowing him to exploit her ignorance and fear for his gain. Caridad faces exploitation as well, both before and after her "holy recovery." She becomes a sexual object, using intimacy to escape her pain. After discovering her spirituality, she permits Dona Felicia and others in her community to exploit her abilities, struggles, and faith for their purposes. Caridad's exploitation ultimately leads to her death. Castillo appears to suggest that exploitation of any form is inescapable for women.

In this novel, religion and dedication to faith are the root of most issues. The main conflicts revolve around how women are expected to navigate a patriarchal religion while maintaining their identity as women. In So Far From God , Catholicism offers no escape for the female characters; they are forced to either submit to male dominance or face death. Both Dona Felicia and, eventually, Sofi reject this type of religion and find liberation from its restrictions, but in doing so, they lose everything they cherish. Caridad attempts to reinterpret her religious beliefs, yet she cannot avoid the impact she has on others. People crowd around her, breach her privacy, and ultimately drive her to view suicide as her only escape....