<p>The human microbiome has emerged as a critical modulator of cancer development, progression, and therapeutic response. Advances in sequencing and functional profiling have revealed that commensal microorganisms—particularly bacteria—interact closely with host immune and metabolic pathways, influencing tumor immunity across multiple cancer types. Dysbiosis of the gut microbiome has been associated with tumorigenesis, immune evasion, and resistance to therapy, while specific microbial taxa and metabolites have been shown to enhance antitumor immune responses. These discoveries have catalyzed the development of microbiome-based therapeutic strategies aimed at reshaping host–tumor interactions. This review summarizes current understanding of the cancer–microbiome axis, with a particular focus on therapeutic interventions that leverage microbial modulation. We discuss fecal microbiota transplantation (FMT) as an early, proof-of-concept approach demonstrating the capacity of the microbiome to restore responsiveness to immune checkpoint inhibitors, while also highlighting its limitations related to variability, standardization, and mechanistic uncertainty. We then examine emerging reductionist strategies, including supplementation with individual bacterial strains, defined consortia, and engineered microbes designed to deliver immunomodulatory payloads directly within the tumor microenvironment. Finally, we explore how microbial modulation interfaces with conventional cancer therapies such as chemotherapy, hormonal therapy, and cellular immunotherapies. Together, these studies illustrate a rapidly evolving field transitioning from correlative observations to mechanistically informed therapeutic design. While significant technical and biological challenges remain, continued integration of microbiology, immunology, and synthetic biology holds promise for translating microbiome-based interventions into safe, precise, and effective cancer therapies.</p>