Simple SummaryThe study discusses the potential of targeting transcription factors (TFs) for cancer therapy and provide a systematic classification of various types of TFs involved in the epithelial–mesenchymal transition (EMT) process based on their DNA-binding domain (DBD) structure and highlights some of the main TFs that have the potential to be cancer biomarkers or targeted therapies. Various strategies for targeting TFs, such as small molecules, RNA interference, and immunotherapies, and examples of drugs currently in clinical trials are listed in this study, providing an insight into the role of TFs in EMT and targeted therapies.AbstractTranscription factors involve many proteins in the process of transactivating or transcribing (none-) encoded DNA to initiate and regulate downstream signals, such as RNA polymerase. Their unique characteristic is that they possess specific domains that bind to specific DNA element sequences called enhancer or promoter sequences. Epithelial–mesenchymal transition (EMT) is involved in cancer progression. Many dysregulated transcription factors—such as Myc, SNAIs, Twists, and ZEBs—are key drivers of tumor metastasis through EMT regulation. This review summarizes currently available evidence related to the oncogenic role of classified transcription factors in EMT editing and epigenetic regulation, clarifying the roles of the classified conserved transcription factor family involved in the EMT and how these factors could be used as therapeutic targets in future investigations.