Energy, disaster management, and underground infrastructure (EDU) constitute the essential backbone of a city, underpinning its survival and functionality. This chapter examines the interconnectedness of these three components, offering policy recommendations through analogies with the human immune system. Drawing inspiration from the immune system’s ability to monitor, detect, and respond to threats, the chapter proposes an integrated EDU system designed to work cohesively in anticipating and mitigating risks such as energy outages, disaster impacts, and infrastructure disruptions. The decentralized nature of the immune system highlights the importance of decentralized energy grids, agile disaster response mechanisms, and adaptive underground networks, all of which contribute to a more resilient urban system. By incorporating continuous feedback, fostering adaptability, and encouraging innovation, the proposed EDU integration enables policymakers to create robust, self-sustaining systems that not only protect urban infrastructure but also empower cities to thrive amid uncertainties, securing long-term sustainability and resilience.