The tumor microenvironment (TME) plays a significant role in tumor progression and cancer cell survival. Besides malignant cells and non-malignant components, including immune cells, elements of the extracellular matrix, stromal cells, and endothelial cells, the tumor microbiome is considered to be an integral part of the TME. Mounting evidence from preclinical and clinical studies evaluated the presence of tumor type-specific intratumoral bacteria. Differences in microbiome composition between cancerous tissues and benign controls suggest the importance of the microbiome-based approach. Complex host-microbiota crosstalk within the TME affects tumor cell biology via the regulation of oncogenic pathways, immune response modulation, and interaction with microbiota-derived metabolites. Significantly, the involvement of tumor-associated microbiota in cancer drug metabolism highlights the therapeutic implications. This review aims to summarize current knowledge about the emerging role of tumor microbiome in various types of solid malignancies. The clinical utility of tumor microbiome in cancer progression and treatment is also discussed. Moreover, we provide an overview of clinical trials evaluating the role of tumor microbiome in cancer patients. The research focusing on the communication between the gut and tumor microbiomes may bring new opportunities for targeting the microbiome to increase the efficacy of cancer treatment and improve patient outcomes.