Intratumoral Microbiota in Fueling Cancer and Steering Treatment Response

ABSTRACT Microorganisms within tumors, also known as intratumoral microbiota, actively shape the tumor microenvironment (TME), influencing cancer progression and treatment response. Research has therefore expanded beyond the gut microbiota to intratumoral bacterial and fungal communities. Advances in low‐biomass sequencing, contamination control, and spatial profiling have made it possible to detect these low‐abundance microbes within the TME and map their marked heterogeneity across cancer types and tissue compartments. However, their origins, causal functions, and clinical relevance remain debated. Here, we summarize contamination‐sensitive workflows and high‐resolution techniques required for low‐biomass tissues, and compare representative taxa in major cancer settings. We further explore microbial origins, taxonomic diversity, and localized interactions with malignant, immune, and stromal cells. We synthesize mechanistic evidence linking intratumoral microbes to genomic instability, epigenetic regulation, oncogenic signaling, metabolic reprogramming, and metastasis. Based on these insights, we evaluate their impact on cancer therapies, alongside emerging microbial interventions and barriers to clinical translation. Ultimately, this review provides a framework for assessing intratumoral microbiota as biomarkers, treatment‐response modifiers, and therapeutic targets, while highlighting the key evidence needed to translate these findings into the clinic.