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Hydrogels, as one of the most feasible soft biomaterials, have gained considerable attention in therapeutic applications by virtue of their tunable properties including superior patient compliance, good biocompatibility and biodegradation, and high cargo-loading efficiency. However, hydrogel application is still limited by some challenges like inefficient encapsulation, easy leakage of loaded cargoes, and the lack of controllability. Recently, nanoarchitecture-integrated hydrogel systems were found to be therapeutics with optimized properties, extending their bioapplication. In this review, we briefly presented the category of hydrogels according to their synthetic materials and further discussed the advantages in bioapplication. Additionally, various applications of nanoarchitecture hybrid hydrogels in biomedical engineering are systematically summarized, including cancer therapy, wound healing, cardiac repair, bone regeneration, diabetes therapy, and obesity therapy. Last, the current challenges, limitations, and future perspectives in the future development of nanoarchitecture-integrated flexible hydrogels are addressed.