Collectively known as the microbiota, the commensal bacteria and other microorganisms that colonize the epithelial surfaces of our body have been shown to produce small molecules and metabolites that have both local and systemic effects on cancer onset, progression and therapy response. To date, most studies focusing on the microbiome have used traditional preclinical mouse models and identified correlative relationships between microbial species and cancer phenotypes. Now, the profound influence of the microbiota on the efficacy of cancer treatments, such as immunotherapies, has begun to be extensively characterized in humans. Paramount to the development of microbiota-based therapeutics, the next challenge in microbiome research will be to identify individual microbial species that causally affect cancer phenotypes and unravel the underlying mechanisms. In this Viewpoint article, we asked four scientists working on the cancer microbiome for their opinions on the current state of the field, where the research is heading and how we can advance our understanding to rationally design microbial-based therapeutics to transform treatment strategies for patients with cancer.