The present article includes systematic update information with recent developments in nanocatalyzed organic transformations with the special emphasis on the use of nanostructured heterogeneous catalysts in multi-component syntheses of structurally diverse drug-like small molecules incorporating medicinally privileged heterocyclic systems. Moreover, the nanocatalyzed transformations included in the article are environmentally sustainable and will provide an access to a diverse range of heterocyclic scaffolds with the use of combinatorial chemistry in the presence of heterogeneous catalysts. The reaction mechanisms involving catalytic facilitation with the interaction of nanostructured catalysts with the reacting molecules have also been included. The nanocatalyzed multi-component reactions included in the article will be important significantly for designing synthetic protocols to synthesize natural product mimetic scaffolds with privileged heterocyclic ring systems. Thus, the present review article will contribute considerably not only to the chemical research, especially organometallics, organic syntheses and catalyses, but also to the drug discovery research with the emphasis on pharmaceutical and medicinal research. The present review article presents a thorough and balanced view of the subject. The present article includes systematic update information relating to the uses of sustainable nanocatalyzed multicomponent reactions in the construction of structurally diverse molecules with medicinally privileged heterocyclic substructures. The article contributes not only to the organic syntheses and catalyses, but also to the pharmaceutical and biomedical research in exploring the future opportunity in drug syntheses. image