The purposes of this study were to describe the impact of metal pollution on the main economic fish species Tilapia nilotica and to assess the potential health risk from consuming this contaminated fish in Egypt. Trace metals, including Ag, Al, Cd, Bo, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, St, V, Zn, and As, were determined in water, Tilapia nilotica, and sediments from the River Nile, Domiate branch, Egypt. Metal concentrations in fish of Al, Cd, Co, Fe, Mn, Pb, V, and Zn (mg/kg dry weight [dw]) and concentrations in sediment of Cd, Co, Cr, Cu, Mn, Ni, Pb, V, and Zn (mg/kg dw) were above the International Atomic Energy Agency (IAEA-407) levels. However, trace metals in river water were still at permissible levels for Egyptian standards. The hazard index (HI) of estimated metal mixtures for intake of Tilapia nilotica (23.37) demonstrated that intake resulted in higher noncarcinogenic risk. In conclusion, the overall problem of metal contamination in fish collected from the River Nile was more serious than postulated to occur in an industrialized and densely populated area. In the light of known risks to public health, environmental protection laws are needed in Egypt.