Tien Giang is a province located in the Mekong Delta region, where the Mekong River originates and has two river mouths flowing into the sea, making it frequently vulnerable to the phenomenon of saltwater intrusion (SWI). This article applies the Mike 11-AD model in conjunction with GIS tools to simulate the level of SWI in the river system of Tiền Giang province under the conditions of the RCP4.5 and RCP8.5 climate change scenarios. The results of hydraulic model calibration and validation indicate a high degree of similarity in phase and amplitude of water level oscillations between calculated and measured data during the dry seasons of 2016 and 2020. The simulation results of salinity levels under various climate change scenarios and sea-level rise (SLR) scenarios reveal a trend of increased salinity intrusion into the inland areas of the rivers. Under the influence of climate change and sea-level rise, there is a tendency for saltwater to penetrate deeper into the interior. In the RCP4.5 scenario, SWI with a salinity of 10/00 has the potential to intrude up to 60-80 km, while 20/00 salinity approaches approximately 55 km, and salinity levels > 40/00 encroach to around 25 km. In the RCP8.5 scenario, SWI with a salinity of 10/00 is capable of advancing up to 75-85 km inland, 20/00 salinity reaches approximately 60-80 km, and salinity levels > 40/00 extend to around 45-55 km.