The intestinal gut microbiota has emerged as a fundamental systemic orchestrator of host immunity and a key determinant of therapeutic efficacy and treatment-related toxicity across diverse oncological modalities. Over the past decade, preclinical investigations and clinical trials have demonstrated that the composition of the intestinal commensal ecosystem dictates host responses to immune checkpoint inhibitors (ICIs), standard cytotoxic chemotherapy, and radiotherapy. Specific immunomodulatory bacterial taxa, such as Akkermansia muciniphila, Faecalibacterium prausnitzii, and Bifidobacterium species, modulate host antigen presentation, induce systemic and intratumoral T-cell infiltration, and synthesize immunologically active metabolites like short-chain fatty acids (SCFAs). Conversely, gut dysbiosis induced by broad-spectrum antibiotic exposure or dietary imbalances compromises survival outcomes and escalates therapy-related toxicities, such as chemotherapy-induced mucositis and immunotherapy-related colitis. This narrative review synthesizes the current clinical and mechanistic evidence linking the gut microbiota to cancer treatment outcomes. Furthermore, we critically evaluate therapeutic strategies aimed at manipulating the gut ecosystem, including donor-derived Fecal Microbiota Transplantation (FMT), next-generation live biotherapeutics, dietary interventions, and selective enzymatic inhibitors, to optimize clinical responses and reduce toxicity in cancer patients.