This study aimed to identify differences in management and cost–benefit characteristics of striped catfish (Pangasianodon hypophthalmus) nursery and grow-out farms in freshwater and brackish water areas in the Mekong River Delta (MRD) of Vietnam. One hundred ten striped catfish farms in both areas (50 nursery and 60 grow-out farms) were stratified and sampled for an interview to determine their management and cost–benefit characteristics. The results indicated that the survival rate and yield of fish nursed in brackishwater farms were higher than those in freshwater farms. Fingerling yields and production costs are positively and negatively correlated (pThe net incomes of freshwater and brackishwater nursery farms do not differ significantly (p> 0.05). The fish yield of brackishwater grow-out farms was significantly lower than that of freshwater farms (p < 0.05). Management and cost–benefit parameters of grow-out farms in freshwater and brackishwater areas, if stocking fingerlings reared in the same areas, were not significantly different (p> 0.05). Water salinity strongly affected disease occurrence in the ponds, especially in nursery farms. In the MRD, to improve the climate-resilient farming of striped catfish, a salinity-tolerant strain is essential for nursery and grow-out farming in areas affected by salinity intrusion.