Nano-catalysts are of special character for the synthesis of organic molecules with high efficiency, and exceptional physicochemical properties. The objective of this study was to present an overview of the literature reports concerning the synthetic strategies supported by nano-catalysts and the biological features of heterocycle-integrated pyridopyrimidine scaffolds. The basic topics include the strategies that were adopted to prepare pyrido[2,3-d]pyrimidines and pyrido[1,2-a]pyrimidines. The synthesis of pyrido[2,3-d]pyrimidines was attained through two-, three-, or four-component reactions. The synthesis of spirocyclic systems, including spiro[indoline-pyridopyrimidine] derivatives and arylation reactions, was investigated. The anticipated mechanisms of the diverse target products, in addition to the preparation of the nanocatalysts, were scrutinized. The privileged antimicrobial characteristics, challenges, literature overview, and future prospectives were consistently investigated.