There is substantial interest in targeted cancer therapies, spurred by recent biomedical research in genomics and oncology. Targeted cancer therapies, in which prevention and treatment of cancer are based on genomic and biologic analyses, hold promise for cancer care. However, the rising costs of such therapies may threaten that promise. In an effort to meet the future challenges of targeted cancer medicine head-on, the University of Pennsylvania convened the Gant Family Precision Cancer Medicine Consortium, a multidisciplinary work group of experts from health care economics, policy, law, regulation, cancer research and medicine, patient advocacy, and the pharmaceutical and insurance industry. The Gant Consortium sought answers to a central question: what approaches should stakeholders take to foster the economic viability and sustainability of targeted cancer drugs? The Consortium literature review was conducted from August through November 2016. The expert committee met regularly from October 2016 to May 2017 to identify points of contention and consensus, outline the issues at the core of sustainable targeted cancer medicine, and inform potential policy recommendations. The literature presented in this report does not include therapies developed afterwards, such as CAR-T. The views expressed in this White Paper reflect the discussions of the Gant Consortium but do not necessarily represent the views of either any individual member or of the Consortium as a whole.