The gut microbiota is involved in a lot of crucial physiological functions and maintains a symbiotic relationship with the host. Lately, in light of new evidences, an unexpected role of commensals has been depicted. Several studies addressing the role of gut microbiota in the immunomodulatory properties of anti-cancer regimens, such as immunotherapy and chemotherapy, reveal that commensals are required to mount complete and efficient antitumor immune responses. Therefore, exploration of microbiota-derived compounds in the future could represent a therapeutic option in the armamentarium of cancer treatments.