This research area develops TEA and optimization frameworks to support the design, scale-up, and deployment of separation processes across water and energy applications. Our methods integrate process-level physics with cost and performance models to identify optimal operating conditions, technology configurations, and investment strategies, with an emphasis on robust operation under variable conditions. Open-source software supports rigorous trade-off analysis and comparison of emerging technologies against conventional processes, lowering barriers for practitioners and researchers. Case studies span seawater and brackish water desalination, water reuse, industrial wastewater recovery, critical mineral extraction, and energy-sector separations, with ongoing work extending TEA frameworks to capture uncertainty in energy prices, material costs, and regulatory constraints.