Polyheterocycles are one of the most desired synthetic targets due to their numerous and valuable applications in various fields. Multicomponent reactions (MCRs) are highly convergent one-pot processes, in which three or more reagents are combined sequentially to construct complex products, with almost all the atoms coming from the starting reagents. In this context, the syntheses of 'heterocycles' via MCR-based processes have been reviewed a number of times. However, there is not a single review (recent or otherwise) covering the synthesis of 'polyheterocycles' via a direct MCR or via a one-pot process involving MCRs coupled to further cyclizations (via ionic, metal-catalyzed, pericyclic, or free-radical-mediated cyclizations). This issue is consequently the main topic of the present review, which considers work from the last decade. The work is categorized according to the key processes involved in the syntheses of polyheterocycles, aiming to give readers an easy understanding of this MCR-based chemistry and to provide insights for further investigations. The reaction mechanisms providing novel elements to these MCR-based methods for the synthesis of polyheterocycles are also discussed.