Saltwater intrusion is a critical natural hazard impacting millions of lives globally, particularly in the Mekong Delta, Vietnam. This study presents a comprehensive approach to assessing saltwater intrusion vulnerability, combining hazard, exposure/sensitivity, and adaptive capacity. We developed a salinity intrusion hazard map using data from 68 monitoring stations and 156 prevention culverts collected on February 23, 2020. Twenty-eight indicators representing exposure, sensitivity, and adaptive capacity were standardized and weighted using the Iyengar-Sudarshan method. Our analysis revealed that 15.74 % of the study area, particularly Mo Cay Bac and Mo Cay Nam districts in Ben Tre province and Dam Doi district in Ca Mau province, exhibits very high vulnerability to saltwater intrusion. These findings provide critical insights for designing effective saltwater intrusion warning systems and implementing targeted disaster risk management strategies in the Mekong Delta. The approach and results are also applicable to similar coastal deltas and regions worldwide, offering a valuable framework for mitigating saltwater intrusion impacts.