Abstract: Core-shell tecto dendrimers (CSTDs) are a kind of superstructured dendrimeric nanoconstructs with relatively high-generation dendrimers as the cores and low-generation dendrimers as the shells. Recently, there is growing evidence that the performance of CSTDs constructed with poly(amidoamine) (PAMAM) dendrimers of different generations as reactive modules are not only superior to that of single-generation dendrimers, but also overcomes some biomedical limitations (e.g., restricted drug loading capacity, limited tumor passive targeting based on enhanced permeability and retention effect) of single-generation dendrimers. Herein, the design of CSTDs for biological imaging, chemotherapy, gene therapy, and combination therapy are reviewed. The current challenges and future development prospects of CSTDs in the field of biomedicine are also analyzed.