The gut microbiota plays a crucial role in human diseases, particularly cancer. Recent studies have highlighted the connections between the gut microbiota and cancer immunotherapy, emphasizing the importance of understanding how the gut microbiota regulates immune responses to enhance precision medicine. This review explores the complex interactions among the gut microbiota, the systemic immune system, and immunotherapy in cancer. It discusses potential interventions to minimize adverse effects and outlines five microbiota-targeted strategies to improve cancer immunotherapy efficacy. The gut microbiota's stability, resilience, and diversity are essential for maintaining health, and its interactions with the immune system are multifaceted. The review covers the roles of the gut microbiota in non-gastrointestinal lymphoid organs, the innate immune system, and adaptive immune components, including lymphocytes, macrophages, dendritic cells, natural killer cells, B cells, CD8+T cells, helper T cells, follicular helper T cells, and regulatory T cells. It also examines the impact of the gut microbiota on the efficacy of various cancer immunotherapies, such as PD-1/PD-L1 inhibitors, CTLA-4 inhibitors, adoptive cell transfer, CpG-ODN therapy, and microbial metabolites. The review concludes by discussing current challenges and future directions in this rapidly evolving field, highlighting the potential of the gut microbiota as a target for precision cancer immunotherapeutics.The gut microbiota plays a crucial role in human diseases, particularly cancer. Recent studies have highlighted the connections between the gut microbiota and cancer immunotherapy, emphasizing the importance of understanding how the gut microbiota regulates immune responses to enhance precision medicine. This review explores the complex interactions among the gut microbiota, the systemic immune system, and immunotherapy in cancer. It discusses potential interventions to minimize adverse effects and outlines five microbiota-targeted strategies to improve cancer immunotherapy efficacy. The gut microbiota's stability, resilience, and diversity are essential for maintaining health, and its interactions with the immune system are multifaceted. The review covers the roles of the gut microbiota in non-gastrointestinal lymphoid organs, the innate immune system, and adaptive immune components, including lymphocytes, macrophages, dendritic cells, natural killer cells, B cells, CD8+T cells, helper T cells, follicular helper T cells, and regulatory T cells. It also examines the impact of the gut microbiota on the efficacy of various cancer immunotherapies, such as PD-1/PD-L1 inhibitors, CTLA-4 inhibitors, adoptive cell transfer, CpG-ODN therapy, and microbial metabolites. The review concludes by discussing current challenges and future directions in this rapidly evolving field, highlighting the potential of the gut microbiota as a target for precision cancer immunotherapeutics.