COVID-19 has dramatically changed people’s mobility behavior patterns and affected the operations of different functional sites. In the context of the successive reopening of countries around the world since 2022, it is crucial to understand whether the reopening of different types of locations poses a risk of widespread epidemic transmission. In this paper, by establishing an epidemiological model based on mobile network data, combining the mobile network data provided by Safegraph website, and taking into account the crowd flow characteristics and the changes of susceptible and latent populations, we simulated the trends of the number of crowd visits and the number of epidemic infections at different functional points of interest after the implementation of reopening strategies. Accordingly, the impact of crowd flow changes under different reopening strategies on the risk of epidemic transmission was judged. The model was also validated with daily new cases in ten metropolitan areas in the United States from March to May 2020, and the results showed that the model fitted the evolutionary trend of realistic data more accurately. Further, the points of interest were classified into risk levels, and the corresponding reopening minimum standard prevention and control measures were proposed to be implemented according to different risk levels. The results showed that restaurants and gyms became high-risk points of interest after the implementation of the reopening strategy, especially the general dine-in restaurants were at higher risk. Religious activity centers were the points of interest with the highest average infection rates after the implementation of the reopening strategy. Points of interest such as convenience stores, large shopping malls and pharmacies were at a lower risk for outbreak impact after the reopening strategy was implemented. Based on this, reopening prevention and control strategies for different functional points of interest are proposed to provide decision support for the development of precise prevention and control measures for different sites.