Pharmacogenomics (PGx) is a leading application of precision medicine. Many gene-drug variant annotations have been reported, and genetic testing is rapidly becoming less expensive. PGx provides a rich opportunity for research because medication response remains highly variable, despite the fact that the pharmacology of most drugs is well understood. However, successful PGx clinical implementation models to drive value-based care and research frameworks for large-scale genotype-phenotype discovery remain elusive. Empeys multidisciplinary research team launched the Pharmacogenomics-guided Care to Improve the Safety and Effectiveness of Medications (PreCISE-Rx) initiative to study PGx clinical implementation, research, and education. The hypothesis is that the prediction of patient medication outcomes by integrating PGx and clinical variables will improve the health of the population at reduced cost. The aims include validation of onsite PGx clinical testing; configuration of electronic health record systems for the storage of discrete, life-long genetic results and clinical decision support; creation of a research framework with simple consent language, bio-banking, and data sharing; and new clinical services with robust drug-use policy governance.