Manzala Wetland is Egypt's largest ecosystem and the country's second-largest lake overall. In 2016, in line with Egypt's Vision 2030, the Egyptian government developed a strategy to boost the economic potential of northern lakes, which includes Manzalah Wetland.  The focus of this research was to test for trace elements including lead (Pb), mercury (Hg), arsenic (As), and aluminum (Al) in the muscle tissue of three commercially significant tilapia fish species gathered with the help of Manzalah Lake fishermen in 2018. Pb and Hg were largely above the permissible level of Food Agricultural Organization FAO, World Health Organization WHO, and Commission Regulation EU.  The proximate chemical composition and antioxidants of the liver were estimated. The results showed that the highest mean carbohydrate, and fats, found in O. aureus, the water content and ash in T. zillii, and protein concentrations were in S. galilaeus. The results of the current investigation showed that S. galilaeus had the highest levels of activity of liver antioxidants CAT, Gpx and GR, SOD in T. zillii, as well asGSH level in O. aureus. The metal with the highest concentration was Pb in O.aureus (2.85±0.2), whereas the least amount was Hg in S. galilaeus (0.55±0.04). Hg levels in O. aureus, S. galilaeus, and T. zillii ingested by children, youth, and adults showed the lowest of all metals, but they were higher than the permissible levels, indicating a risk to people's health from consuming the examined hazardous element through the diet of the three fish species. The target hazard quotient (THQ ) value of As in T. zillii intake by a child demonstrated the highest value ranging from (21 a day to 147 a week), while the THQ value of Pb in S. galilaeus intake by an adult showed the least value of THQ (0.73 a day or 5.11 a week). Based on the values of the total target hazard quotient (TTHQ) of the three fish samples for children, youth and adults, ingesting these fish pose a high non-carcinogenic risk. Tilapia zillii ingested by children recorded the highest degree of carcinogenic risk (CR) (9.45E-03 a day or 6.62E-02 a week); whereas, S. galilaeus in adults recorded the lowest level of CR (2.19E-05 a day or 1.54E-04 a week). The THQs and CRs values of Pb, Al, As, and Hg in the three examined species were greater than one, surpassing the Environmental Protection Agency recommendation (US EPA) acceptable limits. This finding demonstrates that daily or weekly eating of these species could pose a high risk of non-carcinogenic and carcinogenic consequences to humans; thus, the fishes of the lagoon may be dangerous for human consumption in general.