In a perspective piece published in Frontiers in Sustainable Cities, Resolve to Save Lives and partners outline ten key themes for strengthening health security in urban environments. Given cities’ unique vulnerabilities to infectious diseases, the paper highlights areas such as community partnerships, governance and financing, risk communication and resilient infrastructure as critical for epidemic preparedness. By intentionally advancing these themes, cities can better prevent, detect, respond to and recover from health threats—offering a roadmap for enhancing public health resilience in urban settings worldwide.