Anthropogenic development can strongly influence natural river processes, leading to environmental changes that negatively affect important habitats and biodiversity and consequently reduce economically important natural resources. This study investigated the effects of salinity intrusion on the habitat of the clam Corbicula japonica in the Seomjin River estuarine zone. We employed the Environmental Fluid Dynamics Code (EFDC) model, which incorporates topographic data and hydrological changes, to simulate salinity. Two salinity measurement facilities were installed in Seomjin River estuarine and operated to optimize the EFDC model. The results show that reduced flow rates due to intake have a negligible impact on the increased salinity. Maintaining optimal salinity (15–20 psu) during neap tides at the Seomjin River Bridge requires constant high flow rates, which poses significant challenges. Saltwater stratification is identified as the primary cause of pronounced salinity stratification, particularly during neap tides. Addressing this issue through river discharge and intake facility operation is challenging. Structural measures, including riverbed restoration and underwater barriers, are recommended to improve resistance to seawater intrusion. Future research should aim to develop scenarios to reduce salinity, quantify the reduction efficiency, and propose region-specific measures.