G1 to S phase transition 1 (GSPT1, also known as eRF3a) is a crucial translation termination factor that plays a vital role in acute myeloid leukemia (AML) and MYC-driven lung cancer. Degrading GSPT1 can induce apoptosis in cancer cells and reduce their viability, thus making GSPT1 a potential therapeutic target. This perspective aims to introduce the current research status of the mechanism of molecular glues targeting GSPT1, summarize the recent progress in and challenges for existing molecular glues, bifunctional degraders, and antibody-enabled molecular glues targeting GSPT1, and outline the development strategies for targeting GSPT1 in the treatment of cancer.