Gain tells two stories separately and intertwines them. In one story, we're introduced to Laura Bodey, a real estate agent and mother who discovers she has ovarian cancer. In the other, we learn about Clare Soap and Chemical Company, a soap manufacturer that is established in the mid-1800s and grows over the next century.

Laura is divorced and working incredibly hard to make a good life for herself and her children. We meet Laura at a funeral for a teenage friend of Laura's daughter, Ellen. The girl died mysteriously, and the community is distraught. Not long after, Laura's doctor discovers a cyst on an ovary and Laura has it removed. When it turns out to be cancer, Laura has to begin fighting for her family and her life. Her ex-husband, Don, remains a significant part of her life, especially post-diagnosis. He begins to suspect that contaminants from the nearby plant for Clare Soap and Chemical Company may be to blame. Thanks to Don's suggestion, Laura decides to join a class action lawsuit against the company. She ultimately wins and is awarded a financial payoff. Laura passes away, leaving her children devastated.

While Laura's story is the emotional crutch of the novel, the main tale is that of the Clare Soap and Chemical Company. After its establishment by Jephthah and Sarah Clare in 1831, the company begins to grow. An immigrant, Robert Ennis, sells them some candles that they grow to love and hope to sell in their store. They scour the streets for Ennis until they find him again and ask him to join the company.

We watch the company hire an engineer, Anthony Hewitt, to design and build equipment that will economize the manufacturing process. We're also introduced to new members of the Clare family as the novel continues. Samuel Clare purchases the first candles from Ennis and Resolve Clare finds Ennis at the fish market later on. Benjamin Clare heads an expedition to Antarctica where he discoveres an herb that ultimately becomes one of their most successful products, Native Balm.

When the company expands across the country, it is seen as a boon to local economies. Lacewood, Illinois, where the Bodey family resides, asks Clare Soap and Chemical Company to expand there. They are looking for job opportunities for their citizens, and since Lacewood has space and people, a commodity Clare Soap and Chemical Company needed, the deal goes through. The next decades of expansion leads to corners being cut and pollutants being released into the Lacewood community.

Through the story of the development of the Clare Soap and Chemical Company, we see how a small, family-run business developed into a huge organization with multiple priorities and various leaders. That shift is what gave the company the opportunity to pollute as they did. Over time, those at the very heart of the company entrusted aspects of this growth to others, and making money became a larger priority for those people than following environmental protocol. At the end of the novel Tim, Laura's son, decides to use the money from the lawsuit to establish his own business. This moment harkens back to the establishment of the Clare Soap and Chemical Company a century earlier.

As the novel closes, so does Clare Soap and Chemical Company. They sell off their Lacewood plant and shudder its doors. Lacewood, after a century of dependence on the manufacturing industry, is once again a small town. The Bodey family still lives there and even Ellen, who moved away for some years, returns to settle in her hometown.