In aquatic ecosystem biomonitoring, the use of biota and their habitat provides a good indication of conditions and potential threats to any water body. The potential for heavy metal poisoning in humans because of consuming tainted fish has gotten a lot of press around the world. Heavy metal pollutants in water are mostly caused by human activities such as waste disposal, organic fuel combustion, phosphate fertilizers, plastics, and pesticides. The aim of this study was to see how much heavy metals contamination there was in Nile tilapia Oreochromis niloticus and how physicochemical characteristics affected the biomarkers. Heavy metals accumulation (cadmium, lead, zinc, copper, and iron) was studied on the serological indices of a freshwater fish O. niloticus. Fish, water, and sediments were collected at three locations along the Nile River. The findings of this study showed a significant difference in water quality indices in response to pollution levels among the sites studied. Consequently, the current results confirm that the distribution of heavy metals in tissues could potentially deteriorate biochemical parameters of. O. niloticus.