As a leading cause of mortalities worldwide, cancer results from accumulation of both genetic and epigenetic alterations. Disruption of epigenetic regulation in cancer, particularly aberrant ubiquitination, has drawn increasing interest in recent years. The present study aimed to review the roles of ubiquitin-conjugating enzyme E2 T (UBE2T) and its associated pathways in the pathogenesis of pan-cancer, and the development of small-molecule modulators to regulate ubiquitination for treatment strategies. The current study comprehensively investigated the expression landscape and functional significance of UBE2T, as well as its correlation with cancer cell sensitivity to chemotherapy/radiotherapy. Multiple levels of evidence suggested that aberrant UBE2T played important roles in pan-cancer. Information was collected from 16 clinical trials on ubiquitin enzymes, and it was found that these molecules had an important role in the ubiquitin-proteasome system. Further studies are necessary to explore their feasibility and effectiveness as diagnostic and prognostic biomarkers, or as up/down-stream and therapeutic targets for cancer treatment.