The use of precision medicine and the number of genomic-based treatments and immunotherapies is increasing. Nevertheless, oncology providers face challenges to implementing precision medicine, including in community practices, where most patients receive treatment. On January 31, 2018, ASCO hosted Precision Medicine: Expanding Opportunities, the inaugural event in ASCO's new State of Cancer Care in America (SOCCA) event series. This article draws from the inaugural SOCCA event and the experiences of the SOCCA event participants to summarize the opportunities and challenges of precision medicine, and to highlight three successful models of implementing precision oncology in large, multisite community practices or networks: (1) Intermountain Healthcare, (2) Levine Cancer Institute, Atrium Health, and (3) National Cancer Care Alliance. The experience of these practices suggests that practice innovations that offer clinical decision support through molecular tumor boards and clinical pathways, and administrative support for prior authorization and clinical trial matching are key to successful implementation of large-scale, community-based precision medicine programs.