Low-lying coastal regions and their populations are at risk during storm surge events and high freshwater discharges from upriver. An integrated storm surge and flood inundation modeling system was used to simulate storm surge and inundation in the Tsengwen River basin and the adjacent coastal area in southern Taiwan. A three-dimensional hydrodynamic model with an unstructured grid was used, which was driven by the tidal elevation at the open boundaries and freshwater discharge at the upriver boundary. The model was validated against the observed water levels for three typhoon events. The simulation results for the model were in reasonable agreement with the observational data. The model was then applied to investigate the effects of a storm surge, freshwater discharge, and a storm surge combined with freshwater discharge during an extreme typhoon event. The super Typhoon Haiyan (2013) was artificially shifted to hit Taiwan: the modeling results showed that the inundation area and depth would cause severe overbank flow and coastal flooding for a 200 year return period flow. A high-resolution grid model is essential for the accurate simulation of storm surges and inundation.