Disasters and COVID-19 pandemic have a far more negative impact on groups both epidemiologically and socioeconomically in the Asia-Pacific, a region with highest impact on global population (87%) from natural hazards. This policy brief aims at providing a new insight into key recommendations and prospective agenda to rejuvenate vulnerable cities and increase the resilience capacities as a result of systemic risk, emerging hazard, compound disaster driven by extreme weather events, climate change and COVID-19 pandemic. Four priorities are recommended: (1) Assessing new emerging hazards and future systemic risks in the vulnerable area; (2) Strengthening risk governance and communication for rapid decision-making for action; (3) Diversifying investment strategies for local resilience; and (4) Empowering locally-led and nationally-supported disaster risk reduction (DRR) and resilience program. A transdisciplinary approach is promoted to integrate public health and DRR to prevent future pandemic risk, rebuild vulnerable societies, and strengthen resilient cities in an extreme climate.