Cancer is a complicated disease attributed to multifactorial changes, which causes difficulties with treatment strategies. Various factors have been regarded as the main contributors, and infectious etiological factors have recently attracted interest. Several microbiomes contribute to carcinogenesis, cancer progression, and modulating cancer treatment by inducing cancerous epithelial cells and chronic inflammation. Most of our knowledge on the role of microbiota in tumor oncogenesis and clinical efficiency is associated with the intestinal microbiome. However, compelling evidence has also confirmed the contribution of the intratumor microbiome in cancer. Indeed, the findings of clinical tumor samples, animal models, and studies in vitro have revealed that many intratumor microbiomes promote tumorigenesis and immune evasion. In addition, the intratumor microbiome participates in regulating the immune response and even affects the outcomes of cancer treatment. This review summarizes the interplay between the intratumor microbiota and cancer, focusing on the contribution and mechanism of intratumor microbiota in cancer initiation, progression, and potential applications to cancer therapy.