Heavy metal pollution has a harmful impact on the health of all living beings. The goal of this study was to compare the impacts of zinc (Zn), lead (Pb), iron (Fe), and manganese (Mn) on two Egyptian streams in Aswan Governorate. In addition, aquatic Chironomidae larvae were exposed to a variety of heavy metal concentrations for two days. The mortality rate was determined, and the median lethal concentrations (LC50) were estimated. The most harmful metal for Chironomidae larvae was Pb, followed by Zn, Fe, and Mn. Metal bioconcentration in Chironomidae larvae increases with increasing concentrations of metals. The enzymatic response to heavy metals uptake in Chironomidae larvae; namely, lipid peroxidation, superoxide dismutase, catalase, glutathione-S-transferase, and glutathione peroxidase were determined. Although the Pb-treated group recorded the highest lipid peroxidation, it showed the lowest glutathione peroxidase activity. The glutathione-S-transferase enzyme was less active in the Zntreated group, as was the superoxide dismutase enzyme, and the catalase enzyme was the least active in the Zn-treated group. Changes in randomly amplified polymorphic DNA (RAPD) profiles were detected following heavy metal treatments at various doses when compared to controls. This study gives insight into how cruise ship activities and industrial pollution in rivers endanger aquatic life and hence, human life.