<p>Pharmacogenomics provides proactive, mechanistic insights into adverse drug reactions, while pharmacovigilance ensures reactive, real-world monitoring. This article describes their integration into precision pharmacovigilance, a synergistic paradigm that is transforming drug safety. By linking the why of genetic predisposition to the what of population-level outcomes, this approach enables a fundamental shift from problem detection to proactive, personalized harm prevention. Here we explore the digital ecosystem—electronic health records, artificial intelligence and real-world data—that underpins this integration. The clinical potential is illustrated by compelling case studies: preventive HLA-B*15:02 screening has virtually eliminated carbamazepine-induced SJS/TEN in certain populations, and analysis of national databases shows that a small panel of genes could prevent a significant proportion of adverse events. Despite these promising results, widespread application is hampered by systemic hurdles. These include the lack of data standardization, regulatory fragmentation and a critical knowledge gap among physicians that undermines trust and hinders adoption. Unlocking this potential will require a multi-pronged effort across technology, policy and practice. Technologically, the development of trustworthy and explainable artificial intelligence is critical to building trust in the clinic. Policy makers need to establish data standards for interoperability, create clear reimbursement for pharmacogenomic testing, and harmonize regulatory guidelines. Critically, healthcare systems must foster a culture of continuous learning that enables clinicians to interpret and apply genomic data effectively. Removing these systemic barriers can finally close the gap between innovation and implementation and usher in an era of safer, truly personalized medicine.</p>