This chapter presents a comprehensive systems framework for the large-scale integration of transport, energy, and materials (T–E–M) critical to achieving sustainable and resilient urban futures. It begins by outlining the decarbonization imperative, renewable energy challenges, and material supply vulnerabilities, emphasizing the complex multi-timescale dynamics involved. Drawing on immunological analogies, the chapter proposes an innovative “immune strategy” for policymaking, planning, and technological development, framing T–E–M systems as a metabolic body with layered defenses and adaptive capacities. It then introduces an integrated immuno-computational architecture to coordinate real-time and strategic operations, supported by a physical system design that mirrors immune functions such as sensing, metabolism, circulation, regeneration, and cognition. Addressing practical barriers, the chapter discusses governance, business models, technology compatibility, financing, and social equity. Finally, it synthesizes the nine interconnected principles of Urbanimmunology as a guiding framework to operationalize T–E–M integration at scale, advancing a new paradigm of infrastructural intelligence grounded in coherence, adaptation, and regenerative resilience.