Precision medicine now needs to also consider the microbiome in oncology treatment. Ingested substances, whether they are a carcinogenic or therapeutic agent, will likely come into contact with the microbiota. Even those delivered extra-intestinally can be influenced beyond xenobiotic metabolism by biochemical factors associated with the microbiota or by an immunological predisposition created by the microbiome. We need to undertake one of the largest paradigm shifts to ever occur in medicine, that is, every drug or ingested substance needs to be re-evaluated for its pharmacological effect post-microbiome interaction. The importance of the microbiome with a focus on the treatment of cancer is discussed. In the near future, it may be possible to specifically manipulate the microbial composition within cancer patients to improve the therapeutic potential of existing oncological agents. However, the current tools to do so are limited. Targeted modulation is likely to be achieved by addition, selective enhancement or depletion of specific microbial types. This may include compounds such as narrow spectrum antimicrobial agents or oligosaccharides that will kill or enhance the bacterial growth of distinct members of the microbiota, respectively. This will stimulate a new era in these fields.