Inspired by the intelligence of the human immune system, the DIRECT approach offers a transformative framework for managing policymaking process that is both proactive and adaptive. Its six core components—Detect, Inform/Intervene, React, Enlighten/Enforce/Evaluate, Collaborate, and Transfer—mirror key immune functions: threat detection, signaling and response coordination, rapid disruption management, adaptive learning, system-wide collaboration, and knowledge transfer for future resilience and vitality of cities and society. This chapter explores how the DIRECT approach can be applied across sectors, including pandemic response, decarbonization of transportation, and public health promotion. It demonstrates how cities and society can effectively address immediate and potential risks while fostering sustainable, long-term solutions. Moreover, the principles of DIRECT provide a flexible and scalable framework for confronting broader urban challenges such as climate change, social inequality, and infrastructure development. By embedding this approach into policymaking, cities and society can enhance their capacity to navigate evolving challenges, ensuring that policies remain both responsive and forward-thinking in an ever-changing world.