While often described as a "disease of the genes," cancer is, in fact, a complex dynamic system in which evolving cells both affect and are affected by the physical properties of their environment. About 10 years ago, after a number of multidisciplinary workshops and meetings, the NCI leadership embarked on a bold program to systematically integrate physical sciences into cancer biology and treatment through formation of the Physical Sciences-Oncology Network (PS-ON). Here, we highlight key areas in which the two disciplines have been successfully integrated and lessons learned from the first decade of the PS-ON experiment.