The Cape Fear River Estuary (CFRE) region is a coastal domain that has experienced considerable threats and impacts from tropical cyclones. It is also an important nursery for juvenile fish, crabs, shrimp, and other biological species. Thus, predictions about the physical responses of the CFRE system to extreme weather events are important to the protection of life and property and to the economical well-being of local residents. In this study, the Princeton Ocean Model (POM) is used to simulate tropical cyclone storm–induced surge, inundation, and coastal circulation in the CFRE and the adjacent Long Bay using a three-level nesting approach. Hindcasts of the hydrodynamic responses of the CFRE system to historic events were performed for Hurricanes Fran, Floyd, Bertha, and Charley. Comparisons were also made for the modeling results and the observations.