Home to over 80 million people, the US-Mexico border region is a conduit and source of commerce, tourism, and exchange that is vital to both countries. Deep economic ties and an underappreciated history necessitate binational integration and cooperation, especially on issues of shared importance like health, transportation, infrastructure, and scarce natural resources. Population growth, climate change and shifting migration patterns threaten the border region’s resilience, which emphasizes the need for emerging technologies, smart solutions, and innovation to new and long-standing problems. This panel addresses challenges and approaches to cross-cutting themes in physical and cyber security, energy and water, climate, and healthcare, and a cross-national platform for applied solutions.