<p>Fused imidazopyrimidine nucleus constitutes an important class of heterocyclic compounds in organic chemistry. Imidazopyrimidine consists of imidazole and pyrimidine ring, both of which are present in natural products such as folic acid and vitamins. They have gained attention for their diverse photophysical effects and biological properties, making them valuable in agrochemicals, organic fluorescent materials, pharmaceuticals, and medicinal chemistry due to their strong pharmacophoric moiety. Thus, many methodologies have been developed for the synthesis of this important class of compounds. Among these synthetic protocols, the multicomponent reactions provide opportunity to develop new synthetic processes that are ecologically friendly and economically sustainable. But, there remains space to develop greener and simpler protocols based on application of retrievable catalysts or green solvents to accomplish the synthesis of imidazopyrimidine ring systems efficiently. Herein, the recently developed mild, efficient, and environmentally friendly protocols for the synthesis of imidazopyrimidine derivatives via the multicomponent reaction approach, obtaining good yield, and purity are explained. This review comprehensively summarizes various catalytic multicomponent reaction methodologies involving heterogeneous catalyzed synthesis, organo-catalyzed reactions, metal-mediated, base catalyzed, and some other related reaction systems for the synthesis of fused imidazopyrimidine heterocyclic molecular libraries. The aim of this review is to access the advanced multicomponent methods for the formation of fused structures of imidazopyrimidine derivatives during the years of 2020–2025.</p> Graphical Abstract <p></p>