Freshwater scarcity, salinity, and poor soil fertility are the major challenges affecting both food and feed productions in arid and semi-arid regions of the world. Utilization of brackish water in the production of saline-tolerant fish and valuable field crops under an integrated system is promising in the maximization of yield per crop. The aim of this study, therefore, was to (1) assess the effect of saline aquaculture wastewater on the growth, yield, forage quality, and nutritive composition of sorghum seeds and (2) assess the effect of different water qualities on the survival, growth performance, and health status of Pangasianodon hypophthalmus. The experiment was conducted in a randomized completely block design of four salinity treatments with three replicates, i.e., control (freshwater mixed with inorganic fertilizers), 5000 ppm, 10,000 ppm, and 15,000 ppm. Our results indicated that although the control exhibited the highest growth (plant height, leaf number, internode number, leaf area, and soil–plant analysis development), grain, and forage yield, no significant differences were noted among the treatments. Likewise, no significant difference in the grain nutrient composition was noted among all the treatments. Assessment of the forage quality revealed improved crude protein content in the control compared to the saline treatments. However, no significant differences in the leaves and stalks fiber fractions were noted among all the treatments. Furthermore, rumen fermentation in terms of in vitro digestibility indicated no significant differences in the in vitro digestible dry matter, digestible organic matter, metabolic energy, net energy, microbial protein, short-chain fatty acids, and total dissolved nutrients among the treatments. However, rearing P. hypophthalmus in water salinities exceeding 10,000 ppm reduced the growth performance and health status of fish. Therefore, the integration of sorghum and P. hypophthalmus production in water salinities not exceeding 5000 ppm is a viable alternative to maximize brackish water productivity in freshwater-scarce regions.