Abstract: Core megacities, characterized by large population base, high population density, frequent domestic and international population and material movement, as well as complex social structures and spatial environments, have become the key areas in the prevention and control of emerging infectious disease (EIDs), especially the prevention and control of imported infectious disease, respiratory infectious disease, and vector-borne infectious disease. The epidemics often exhibit characteristics of concealed transmission, multi-point outbreaks, and difficult source tracing, posing serious challenge to early detection, epidemiological investigation and tracking, quarantine and control, and resource allocation. The existing infectious disease prevention and control system has shortcomings of fragmented surveillance, static risk assessment, reliance on empirical early warning, and mis-resource allocation. For the purpose of “early detection, early warning, and early intervention,” there is an urgent need to construct a key technical toolkit for the intelligent prevention and control of EIDs characterized by “data-model-decision” structure for core megacities.The design of the toolkit should follow the principles of scientificity and systematicity, data-driven and intellectualization, user and scenario-friendliness, integrated peacetime and wartime use, and dynamic iteration. The toolkit should comprise foundational support layer, multi-source sensing layer, intelligent analysis and early warning layer, and decision-making coordination layer to facilitate the prevention and control from passive response to proactive warning and intervention through technology integration, and provide a systematic technological solution to improve public health resilience in core megacities.