Water resource scarcity, variability, and uncertainty are becoming more prominent both domestically and internationally. Because energy and water are interdependent, the availability and predictability of water resources can directly affect energy systems. We cannot assume the future is like the past in terms of climate, technology, and the evolving decision landscape. These issues present important challenges to address. While many federal agencies are engaged in the water-energy nexus, the U.S. Department of Energy (DOE) can play an important role by bringing more science, technology, and analytical capability to the water-energy nexus, drawing on expertise in research and development (R&D) programs, and engaging the strengths of the national labs. In addition, many issues surrounding the water-energy nexus affect assets owned and operated by private sector entities; development of public-private partnerships can help leverage DOE capacity. This Water-Energy Nexus: Challenges and Opportunities report builds on the Department‘s previous work in this area and provides a foundation for future DOE action in response to the challenges before us. This report presents extensive data and analysis to frame the opportunities. This report is also intended to encourage others to engage in a dialogue and work together to address the challenges. Systematically and proactively addressing the water-energy nexus will help us all ensure a reliable and sustainable energy system.