This study evaluated inundation impacts and the economic damage resulting from sea level rise (SLR) in the Vietnamese Mekong River Delta (VMRD), and identified the effectiveness of mixing gray and green infrastructures using cost-benefit analysis. The results showed that the VMRD could potentially be heavily affected by SLR. Without the implementation of proper adaptations, more than 90% of this area could be below sea level and nearly 20 million people could be affected by inundation by the end of the 21st century. The total economic damage could reach more than 22,000 billion US$ (2010 real value) by 2100 with no discount rate. These threats may increase the pressure on the region to ensure well-being, equity, and progress towards achieving sustainable development goals. However, achieving these goals will require the implementation of adaptations for upgrading and restoring in the region. This study assessed the effectiveness of adaptations and demonstrated that mixing gray and green infrastructures could benefit coastal inhabitants at a cost of 12 to 19 billion US$.