Abstract: The gut microbiome, known as the second genome of the human body, displays correlations with several diseases in humans. Accumulating evidence supports close correlations between the gut microbiome and the occurrence, development, and response to treatment of tumors. The emergence of immunotherapy has improved the current situation of tumor treatment. However, relatively few patients respond optimally to immunotherapy. Most patients still do not benefit from immunotherapy. Immunotherapy has entered a bottleneck period. Research show that the gut microbiome can enhance the efficacy of immunotherapy through a variety of mechanisms and also provide markers for predicting immune response. In addition, the gut microbiome can reverse immunostimulatory drug resistance in tumors and alleviate immunostimulatory drug-related toxicity in the host body. Research focused on the gut microbiome is expected to provide new methods to overcome the limitations of cancer immunotherapy. This review summarizes the latest progress in research correlating the gut microbiome with tumor immunotherapy.