Multi-Scale Sustainable Energy Systems Engineering introduces a unified framework for modeling, analyzing, and optimizing complex energy systems, emphasizing interconnections across materials, processes, and sectors to accelerate future energy pathways and the energy transition. The book covers advanced mathematical algorithms, uncertainty management, machine learning, and life cycle assessment, supported by real-world case studies like renewable hydrogen production. Readers will find detailed methods for designing large-scale energy solutions such as power-chemical polygeneration, renewable integration, and supply chain planning, along with considerations for dynamic, environment-aware operations. The final sections explore the food-energy-water nexus and provide practical tutorials using the ENERGIA software platform. This self-contained resource empowers researchers, engineers, policymakers, and graduate students to develop innovative solutions for sustainable energy challenges and contribute meaningfully to the transition towards cleaner, more resilient energy systems.