The main themes of Gain by Richard Powers are entrepreneurship, capitalism, power dynamics, community, and family.

Entrepreneurship and capitalism go hand-in-hand throughout the novel. When the Clare family starts their business, they are trying to pull together to support their family. It starts very small, with imported supplies, and grows over the course of the 1800s and 1900s into a huge conglomerate. The larger the company grows, and the more non-family members join the leadership team, the more that capitalism takes over the narrative of the Clare Soap and Chemical Company story. Later in the novel, when Tim prepares to start his own business, the fear hanging in the air is that capitalism might take over his business the same way it once took over the Clare family's business.

The power dynamics at play between the huge corporation that has taken over Lacewood and the citizens of the town are prevalent in the narrative. Lacewood residents are told the company will revitalize their economy and present them with the American dream. The reality is much more bleak. The Clare Soap and Chemical Company has control and autonomy in the town and uses it to take advantage of the Lacewood citizens. Due to the negligent nature of the Clare company, citizens of Lacewood get sick and, in some cases, die.

The community of Lacewood, Illinois fights for the opportunity to bring the Clare Soap and Chemical Company to their town. They hope that the new business will provide jobs and opportunity for the Lacewood residents. Once the company is established, and people begin to get sick, the residents again come together to sue the company and ask for their lives back. Centuries earlier, as Clare began to expand, they often went to places like Lacewood to offer communities respite from hard financial times. The intentions of the Clare company were good, even if the ultimate results were bad.

Family is a central theme in the novel. Generations and generations of Clare family members work to establish, grow, and ultimately shutter the business. They each bring different skills to the table that benefit the company and help it to increase revenue. Laura and Don, however, come together to fight Laura's cancer and participate in the lawsuit against the Clare company.