Increased saltwater intrusion likely causes a significant reduction in food production in alluvial river deltas worldwide. One of the mitigation measures for saltwater intrusion is to increase natural flow through irrigation water conservation and land-fallowing policies to prevent the saltwater from moving further inland. However, economic estimates of the costs of such measures under uncertainty are scant. Herein, we develop an integrated modeling framework for estimating the costs of saltwater intrusion mitigation policies by 2050 in the Mekong Delta. The integrated model combines hydrodynamic, advection-dispersion, statistical, crop yield, and economic models, thus allowing us to account for the risk and uncertainty of saltwater intrusion and the costs of mitigation policies. We found that a 95% confidence interval of the saltwater intrusion-impacted area is estimated to be 186,000-201,000 hectares for the baseline, 193,000-209,000 hectares for a sea level rise of 22 cm, and 204,000-219,000 hectares for a sea level rise of 53 cm scenarios, respectively. To bring the saltwater intrusion under the sea level rise of 22 cm back to the baseline level, 100,000-150,000 hectares of currently cultivated rice would need to be fallowed at least once a year. This is equivalent to annual economic losses, with a 50% chance, ranging from $100.03-$176.67 million, implying a substantial economic cost of sea level rise-induced saltwater intrusion even under a modest sea level rise scenario. Under the sea level rise of 53 cm scenario, the results show that widespread adoption of alternate wetting and drying and approximately 300,000 ha of land-fallowing would be needed to push saltwater intrusion back to the baseline level. The findings indicate that saltwater intrusion in the Mekong Delta is more likely than not to intensify considerably and is much less predictable, posing a greater risk to one of the most important rice-producing regions in the world.