The beauty of cascade reactions to bestow us with cumbersome organic scaffolds has made them a cutting-edge area of research. Although the planning of cascades may require intuition, their results can be highly impactful. The development of cascades to provide specific targeted molecules of an appropriate structural and stereochemical framework poses a significant challenge but can serve as one of the most impressive tools in organic synthesis. This review shares a broad interest in compiling cascade transformations towards the construction of polycyclic frameworks, induction of chirality/asymmetry in the protocol, etc. to solve diverse challenges in organic synthesis pursuits, as cascades enable the rapid and efficient construction of complex architectures from simple molecules. The studies highlighted herein manifest the utilization of a range of cascade reactions under various classifications for generating natural product skeletons such as palau'amine, benzosimuline, arcutinine, and others from simple building blocks, with emphasis on breakthroughs and potential for asymmetric synthesis. The exquisite synthetic designs of recently completed total synthesis of natural products with a focus on strategic concerns are also highlighted in this review.