Precision medicine is a rapidly evolving paradigm powered by emerging technological, diagnostic, and pharmacological capabilities.  The clinical application of precision medicine holds promise across medical disciplines, and has become increasingly prominent in advanced cancer patients where genomic analyses can readily identify actionable somatic variants.  In spite of the clinical potential of precision cancer medicine, widespread implementation has been limited, largely due to the paucity of robust clinical experience in the space.  Leveraging the unique aspects of a large, integrated health delivery network, we have clinically implemented a comprehensive precision medicine program for advanced cancer patients.  We outline the Precision Cancer Genomics Program at Intermountain Healthcare, and provide insights into the successes, challenges and economic impact associated with the de novo implementation of an enterprise-wide precision medicine program.