This study aimed to evaluate the effects of toxic metals (Cu, Fe, Ni, Cd and Pb) on Burullus Lake water and Oreochromis niloticus. To assess contamination grade and associated eco-toxicological risk use Bio-Concentration Factor (BCF), Contamination Factor (CF), Pollution Load Index (PLI), and Metal Pollution Index (MPI) and in addition to the effect of toxic metals on water quality and fish performance in sixteen sampling sites across the lake. Results revealed a significant (p<0.05) lower heavy metals concentration in water, liver and muscles in eastern sector (ES) compared to other sectors. While, middle sector (MS) showed significant (p<0.05) lower BCF of Fe in liver and muscle. The ES showed the lowest CF, PLI and MPI values in water, liver and muscles except for Fe in muscle CF. Furthermore, ES recorded the lowest salinity, conductivity, total dissolved salts, total ammonia and un-ionized ammonia and the highest dissolved oxygen. Moreover, ES showed the highest fish body weight (p>0.05) and condition factor and the lowest hepatosomatic index (p<0.05). In conclusion, there was a variation in heavy metals content in different sections of the Burullus lake water, ES showed lower heavy metals concentration in water, liver and muscles compared to other sectors. MS showed significant lower BCF of Fe in liver and muscle. The ES showed the lowest CF, PLI and MPI values in water, liver and muscles except for Fe in muscle CF. The ES may consider the lowest contaminated area of Burullus Lake and consequently showed better water quality and fish performance.