•MOF nanoshell materials are “star” platforms in biomedicine.•Preparation strategies of MOF nanoshell materials are systematically reviewed.•Drug delivery, biosensing, bioimaging and cancer therapy are involved.•Challenge and future development are prospected. The integration of metal-organic frameworks (MOFs) and nanoshells to construct MOF nanoshell structures offers promising therapeutic platforms for biomedical applications. These MOF nanoshells, which encompass hollow-shells, core-shells, and yolk-shells, exhibit not only the inherent benefits of MOFs, such as large specific surface area, high pore volume, adjustable pore size, rapid cargo transfer and diffusion, excellent biocompatibility, and biodegradability, but also the structural advantages of nanoshells, including a large cavity, high loading capacity, and protective effects. Consequently, MOF nanoshells emerge as ideal materials for biomedical applications. The incorporation of functional nanoparticles or chemotherapeutic molecules with MOF nanoshells enables multi-component synergy due to their adjustable structures, components, and surface modifications, an aspect unattainable by single-component materials. This review article systematically introduces the synthesis strategies for various MOF nanoshells and delves into their applications in biomedicine, including drug delivery, biosensing, bioimaging, and cancer therapy. Finally, the challenges, suggestions, and future prospects of MOF nanoshell structures are discussed.