Hollow multishelled structure (HoMS), a promising and complex multifunctional structural system, features at least two shells that are separated by internal voids. The unique structure endows it with numerous advantages including low density, high loading capacity, large specific surface area, facilitated mass transport, and multiple spatial confinement effect. In the past twenty years, benefiting from the booming development of synthesis methods, various HoMS materials have been prepared and show promising applications in diverse areas. HoMS has gradually developed into one of the frontiers of materials and chemistry science, attracting extensive attention from many scientists. In this review, the synthesis chemistry of HoMS and its diverse compositions and structures are systematically introduced, the unique properties of “temporal-spatial ordering” and “dynamic smart behavior” of HoMS are highlighted, and the applications of HoMS in energy storage, catalysis, electromagnetic wave absorption, drug delivery and sensor are fully shown. We hope to reveal the intrinsic relationship between the precise synthesis of HoMS and its tunable composition and structural features. We hope the exploration of frontier scientific concepts and phenomena in HoMS research can provide inspiration for its future direction, and promote the flourishing progress of HoMS.