In this study, the effects of heavy metal pollution on three aquatic habitats in the Aswan Governorate of Egypt - Lake Nasser, Aswan Reservoir, and the River Nile - were evaluated for the Nile tilapia (Oreochromis niloticus). 36 water and 90 fish tissue samples were tested for the presence of Cu, Fe, Pb, Cd, and Zn, among other heavy metals. Significant regional and seasonal variations were noted, with the River Nile exhibiting the highest levels of contamination, particularly for lead (Pb), beyond permissible limits in summer. Particular accumulation showed that the largest concentrations of metals were found in the liver and gills, highlighting their roles as the primary organs for detoxification and filtration. Hematological testing showed that exposure to heavy metals significantly changed blood parameters. Significant changes in hemoglobin concentrations, mean corpuscular volume, and red blood cell count point to potential anemia and physiological stress in fish. Seasonal variations were evident, with the greatest changes in hematological indicators occurring in summer and fall. Significant site-specific changes were found by biochemical tests. Higher concentrations of uric acid, creatinine, and liver enzymes such as glutamic pyruvic transaminase (GPT) and glutamic-oxaloacetic transaminase (GOT) in fish from the River Nile suggested compromised kidney and liver function, but higher amounts of these biomarkers were also found in Lake Nasser and the Aswan Reservoir, albeit to a lesser extent, highlighting the problem's pervasive nature and the pressing need for action. These results highlight how vital it is to continue monitoring heavy metal contamination in these aquatic habitats and to control it effectively. In order to lower heavy metal concentrations, the report fervently supports the installation of sophisticated wastewater treatment facilities and strict pollution control measures. Public awareness campaigns are equally vital since they play a critical role in informing the local community about the health concerns associated with eating fish from contaminated streams. This study emphasises the serious risks that heavy metal deposition poses to public health and the environment in freshwater ecosystems, underscoring the significance of sustainable management practices.