Egypt, one of the world's biggest producers of cultured tilapia, is facing significant challenges in using drainage water for aquaculture due to the lack in freshwater. The current study was conducted to evaluate the effects of drainage water treatment on the growth and flesh quality of the Nile tilapia (Oreochromis niloticus), raised on five distinct fish farms in the El-Fayoum Governorate and irrigated with various drainage water sources. Fish growth characteristics, flesh quality, irrigation resources, drainage canals, and water quality of the investigated fish farms were all investigated. The Dayer El-Berka fish farm had the highest values of pH, total hardness, total alkalinity, salinity, and total ammonia, demonstrating the negative effects of the untreated drainage water on aquaculture water quality. All farms, with the exception of Dayer El-Berka and El-Bats fish farm (earthen pond), which showed a high lead content, had copper concentrations below detection limits. Wadi Al-Raian fish farm was recorded with higher cadmium concentrations. The El-Bats fish farm (concrete pond), which is watered with El-Bats drain's treated drainage water, showed the lowest levels of heavy metals. The maximum growth performance was found in the Nile tilapia raised on Wadi Al-Raian and Al-Wadi fish farms, whereas the lowest growth performance was found in Dayer El-Berka fish farms, according to productivity metrics. The current study's findings indicate that fish raised on farms that use treated drainage water for irrigation have great growth rates, superior meat quality, and safe flesh for human consumption.