The study aimed to evaluate the ability of the red tilapia (Oreochromis sp.) to withstand varying unionized ammonia and water salinity levels on growth performance, feed utilization, and physiological state. Three distinct unionized ammonia concentrations of 0.15, 0.20, and 0.25mg/ l and two different levels of water salinity of 25 and 30ppt were assigned in six treatments (T1 through T6), each with three replicates. Eighteen aquariums held a total of 180 red tilapia distributed equally among them. Ten fish were placed at random in these aquariums, with an average initially body weight of 19.42± 0.04g and an initial body length of 8.48± 0.51cm. The experimental fish were fed commercial feed (30% crude protein) at a rate of 3% of their total biomass three times a day, at 08:00, 13:00, and 18:00, for 8 weeks. Blood samples were taken from five fish in each aquarium at the end of the trail to measure the hematological and biochemical parameters. The findings show that the interaction between unionized ammonia and the water salinity had no discernible effect on the majority of growth and feed utilization indices. WBCs, platelets, and MCHC levels were highest in T5, T3, and T4, respectively. T1 had the highest globulin value and urea contents, while T2 recorded the greatest values of liver enzymes ALT and AST. The current study suggests that different unionized ammonia levels affected fish health and quality, but water salinity decreased these effects slightly and allowed the red tilapia to grow well in high salinity water.