Humanity is reliant upon the physical resources and natural systems of the Earth for the provision of food, energy, and water. It is becoming imperative that we determine how society can best integrate across the natural and built environments to provide for a growing demand for food, water and energy while maintaining appropriate ecosystem services. Factors contributing to stresses in the food and energy and water (FEW) systems include increasing regional and social pressures and governance issues as result of land use change, climate variability, and heterogeneous resource distribution. Interconnections and interdependencies associated with the FEW nexus create research grand challenges for understanding how the complex, coupled processes of society and the environment function now, and in the future. To meet these grand challenges, there is a critical need for research that enables new means of adapting to future challenges. The FEW systems must be conceptualized broadly, incorporating physical processes (e.g., built infrastructure and new technologies for more efficient resource utilization), natural processes (e.g., biogeochemical and hydrologic cycles), biological processes (r.g., agroecosystem structure and productivity), social/behavioral processes (e.g., decision making and governance), and cyber-components (such as sensing, networking, computation and visualization for decision-making and assessment). Investigations of these complex systems may produce discoveries that cannot emerge from research on food or energy or water systems alone. It is the synergy among these components in the context of sustainability that will open innovative science and engineering pathways to produce new knowledge, novel technologies and predictive capabilities to solve the challenges of scarcity and variability.