Recent technological advances continue to expand the universe of big data in biomedicine along the four axes of variety, veracity, volume, and velocity, fueling innovations in research and discovery while transforming care delivery. These advances allow quantitative capture of multimodal health, behavioral, social, and environmental data from n-of-all in near real-time to support the development of new therapies and personalization of treatment decisions for the n-of-one. Application of advanced analytical methods, including artificial intelligence and machine learning, to these modern data assets can greatly propel our understanding of health and disease, accelerating the development of safer and more effective anticancer therapies. In this perspective, we rationalize the creation of a universally accessible digital highway system as a foundational infrastructure to enable data fluidity in an equitable manner. An interoperable and integrated digital inter-state highway can facilitate efficient derivation of insights from biomedical big data to improve health outcomes and ensure that the U.S. remains at the leading-edge innovations in technology, advanced analytics, and precision medicine.