In recent years, the use of poly(amidoamine) (PAMAM) dendrimers of different generations as building blocks or reactive modules to construct core-shell tecto dendrimers (CSTDs) that are superior to the performance of single-generation dendrimers has received great attention in the field of biomedical applications. The CSTDs are always based on high-generation dendrimers as the core and low-generation dendrimers as the shell; not only do they have excellent properties similar to single high-generation dendrimers, but they also have overcome some of the shortcomings (e.g., limited drug loading capacity or enhanced permeability and retention effect due to small size) of single-generation dendrimers in biomedical applications. Herein, the recent advances of CSTDs synthesized by different approaches as nanoplatforms for different biomedical applications, particularly for chemotherapy, gene delivery, and combination therapy, as well as biological imaging, are summarized. In addition, the current challenges and future perspectives of CSTDs are also discussed.