In cancer biology, the microbiome has emerged as a revolutionary field, revealing host–microbe interactions that drive cancer initiation, development, metastasis, and therapeutic response. The microbiome plays a mechanistic role in carcinogenesis by directly regulating host cell proliferation, apoptosis, and genomic stability, and indirectly through immune regulation and chronic inflammation. Depending on the microbial genetic makeup and host environment, microbial genotoxins, metabolites, and signaling molecules can either induce tumor growth or exert beneficial anticancer effects. Infectious agents are estimated to trigger a significant proportion of cancers globally, although the mechanistic pathways of the broader microbiome remain less well quantified. Likewise, it has been shown that microbiomes modulate the toxicity and efficacy of cancer treatments—specifically immunotherapy and chemotherapy—by mediating anti-tumor reactions and altering drug metabolism. Microbiome-based diagnostics, predictive markers, and therapeutic strategies like dietary modifications, probiotics, synthetic microbes, and fecal microbiota transplantation have collectively benefited from these breakthroughs. Despite rapid progress, integrating microbiome research into oncology is hindered by patient variability, methodological hurdles, and the difficulty of identifying definitive causal links. Large-scale clinical trials are essential for verifying the functional impact of microbiome-targeted treatments. The current review evaluates the mechanistic influence of microbiomes on cancer diagnosis and therapeutics.