Given the ever-increasing number of colorectal cancer (CRC) survivors, development of new approaches to improve patients’ long-term survival outcomes is a high priority. Recent striking success of immunotherapies in specific clinical circumstances has motivated research to identify novel strategies based on immune modulation to more effectively harness the immune system to combat cancer. Increasing data indicate a considerable influence of diet and lifestyle on CRC prognosis. In turn, diet and lifestyle shape the gut microbiota, which has been associated with CRC incidence and progression and predicts responsiveness to immunotherapy.