<p>A rapidly developing field of personalized medicine is pharmacomicrobiomics, which studies inter-individual diversity in the human microbiome and its effects on medication disposition, effectiveness, and toxicity. The gut microbiota is viewed as a dynamic second genome that can influence drug absorption, distribution, metabolism, and excretion either directly or indirectly, building on pharmacogenomics. This review summarizes the current understanding of the mutually reinforcing interactions between medications and the gut microbiota, including enterohepatic recycling, microbial enzymatic biotransformation, bioaccumulation, and host metabolic regulation. Clinical problems involving prodrugs, chemotherapeutics, immunosuppressants, and endocrine treatments are also covered, along with examples of drug activation, inactivation, and toxicity caused by the microbiota. Pharmacomicrobiomics research can benefit from a quick review of analytical tools, including 16S rRNA sequencing, shotgun metagenomics, and downstream bioinformatics pipelines. Probiotics, prebiotics, enzyme inhibitors, and fecal microbiota transplantation are among the therapeutic strategies for microbiome modification that are examined, with the objective of integrating microbiome profiling into precision medicine paradigms. Pharmacomicrobiomics is a useful advancement in pharmacogenomics and microbiome research that presents a special chance to forecast medication response, minimize side effects, and provide individualized treatment.</p> Graphic Abstract <p></p>