Abstract: Targeted protein degradation technologies break through the limitations of traditional small-molecule drugs against "undruggable" targets, offering novel intervention strategies for cancer, neurodegenerative diseases, and other disorders. Proteolysistargeting chimeras（PROTACs） and molecular glues, with their unique ubiquitin-proteasome system regulatory mechanisms, have emerged as highly promising protein degradation approaches. Immunomodulatory drugs（IMiDs） not only serve as E3 ubiquitin ligase ligands but also possess intrinsic molecular glue properties that induce ubiquitination and degradation of neo-substrates, exhibiting a unique dualdegradation capability. By integrating the precise targeting capability of PROTACs with the neo-substrate reprogramming properties of molecular glue degraders, PROTAC/IMiD bifunctional degraders can be designed to achieve multi-pathway synergistic therapeutic effects through the co-degradation of proteins of interest（POIs） and neo-substrates. Representative molecules, such as NX-2127 and KT-413, have demonstrated unique potential in preclinical and early phase clinical trials to overcome drug resistance and enhance therapeutic efficacy. With systematic exploration of E3 ubiquitin ligases and in-depth analysis of multi-target synergistic pharmacological mechanisms,these bifunctional degraders have enabled successful targeting of some "undruggable" proteins, providing an advantageous strategy for overcoming clinical challenges such as complex disease resistance. This article reviews the research advances in bifunctional degraders based on PROTACs/IMiDs.