<p>The interplay between inflammatory bowel disease pharmacotherapies and the gut microbiota is increasingly recognized as a pivotal factor influencing treatment efficacy and patient outcomes. This review provides a comprehensive and up-to-date synthesis of the bidirectional interactions between inflammatory bowel disease drugs and gut microbiota, emphasizing the emerging field of pharmacomicrobiomics and associated therapeutic implications. Emerging evidence reveals that microbial composition and function not only shape drug metabolism, bioavailability, and efficacy, but are themselves profoundly altered by pharmacologic interventions. In addition to traditional oral drugs and biological therapy used in inflammatory bowel disease, recent approvals of Janus kinase inhibitors, sphingosine-1-phosphate receptor modulators as well as late-stage developmental drugs indicate that drug–microbiota interactions may increase in prominence. Understanding these intricate interactions offers significant potential: microbial signatures may help guide therapeutic decisions as companion diagnostic tools, helping clinicians predict the therapeutic outcome. Moreover, targeted manipulation of the microbiota may open entirely new avenues to complement and enhance the effectiveness of established inflammatory bowel disease therapies. By illuminating current knowledge, knowledge gaps, and future research directions, this review underscores the potential of integrating pharmacomicrobiomic insights into the next generation of personalized inflammatory bowel disease care.</p>