Abstract The intratumoral microbiome has emerged as an important regulator of tumor biology and antitumor immunity, influencing disease progression and responses to cancer therapy. Microbial communities within the tumor microenvironment can interact with immune cells, cancer cells, stromal components, and therapeutic agents, creating a complex microbiome–immune network. Dysbiosis may promote immune suppression through altered cytokine signaling, impaired antigen presentation, metabolic reprogramming, and recruitment or activation of immunosuppressive cell populations. These mechanisms can contribute to T-cell dysfunction, resistance to immune checkpoint inhibitors, and reduced efficacy of chemotherapy, radiotherapy, and other systemic treatments. Conversely, specific microbial taxa and their metabolites may enhance antitumor immune responses and improve therapeutic sensitivity. Understanding the molecular mechanisms underlying intratumoral microbiome–immune crosstalk may therefore provide new opportunities for precision oncology. This review summarizes current evidence on the composition and functional role of the intratumoral microbiome, its interactions with the immune microenvironment, and its contribution to immune suppression and therapeutic resistance. Emerging microbiome-based strategies, including microbial modulation, probiotics, targeted antibiotics, and combination approaches with immunotherapy, are also discussed.