Pharmacogenomics, the study of how genetic variations influence an individuals response to drugs, lies at the core of personalized medicine. By elucidating the genetic determinants of drug efficacy and toxicity, pharmacogenomics offers the potential to tailor drug therapy to each patients unique genetic profile. This review provides a comprehensive overview of the current state of pharmacogenomics and its applications in personalized medicine. We explore the genetic basis of drug response, pharmacokinetic and pharmacodynamic factors, and the techniques for pharmacogenomic testing. Key applications across various therapeutic areas, including oncology, cardiovascular diseases, psychiatry, and neurology, are highlighted. We also discuss the barriers to implementation, such as clinical decision support tools, education, ethical and legal implications, and reimbursement challenges. Finally, we examine future directions, including the integration of pharmacogenomics with other omics data, artificial intelligence, regulatory developments, and direct-to-consumer genetic testing. Overcoming the challenges and realizing the promise of precision therapeutics will require a concerted effort from various stakeholders, continued research, and collaborative efforts to translate pharmacogenomic discoveries into clinical practice.