The dynamic interplay between resident microbiota, host immunity and anti-cancer therapy has generated a captivating enigma underlying the assignment of cause-effect relationships among these factors. The diverse effects of microbes on carcinogenesis, ranging from preventing or promoting cancer to dictating therapeutic outcomes, complicates the understanding of the relationship between the microbiota and the host. Understanding how host-microbe interactions are influenced by genes and environment in carcinogenesis, and applying that knowledge for cancer detection and treatment are gathering prime interest. This review scrutinizes the host-microbe relationship in the context of cancer by discussing the latest findings involving the host-microbe-drug interaction axes.