The present study was conducted to evaluate the pollution phytoremediation capacity and pollution tolerance of Solanum nigrum in two habitats varied in their pollution intensity with heavy metals. We investigated the relative contributions of the hyperaccumulator S. nigrum in eliminating some pollutants from agricultural soils such as Zn, Pb, Ni and Cd in Tanta and in the sewage water irrigated area at El-Gabal El-Asfar (GA) region. The study also concluded that heavy metals pollution resulted in a significant amendment in the primary and secondary metabolic pathways of the plant. The exposure of S. nigrum to heavy metals pollution in GA region resulted in a relative accumulation in soluble sugars, soluble proteins and free amino acids in the plant root, stem and leaves, but their levels in berry were to some extent inferior to those of Tanta region. In addition, the exposure of S. nigrum plants to sewage water effluents in GA region improved the accumulation of osmoprotectant and antioxidant molecules such as proline, glycine betaine, flavonoids and phenolic compounds. Moreover, the medicinally active alkaloids have accumulated in response to sewage irrigation in various organs of GA region plants comparable with those of Tanta region.