The Nile River islands are recognized as the most productive lands in Egypt. Although, these islands are vulnerable to several natural and man-made crises. The present study was aimed to evaluate the consequences of different anthropogenic activities on the heavy metals load and histological alterations in O. niloticus and S. galilaeus collected from four different Nile River islands along the Great Cairo sector (Egypt), and the possible health risks for human consumers. Metals were accumulated in both fish muscles in the following order: Fe > Zn > Cu > Mn > Pb. S. galilaeus was recorded higher metal pollution index than O. niloticus, while El-Warrak Island was documented the highest MPI and hazard quotient among all sampling sites. All sampled tissues were recorded histopathological lesions in both fish. The present study may be considered as an early alert for habitual consumers, particularly at high consumption rates of some fish species.