This article discusses the role of epithelial mesenchymal transition (EMT) and addresses the scientific merits on epigenetic regulation of EMT. The importance of EMT as a prognostic biomarker is explored and the rationale on application of multitargeted epigenetic therapy is discussed. We describe a literature review of the epigenetic influence of such process and we present a potentially effective method to reverse the epigenetic switch in favor for MET, in a clinical setting. A case series of advanced solid tumors are summarized aiming at generating hypothesis for the future recommendations for clinical trials targeting the tumor’s biological behavior through inhibition of EMT. Hypothesis: We propose an integral and integrative approach that can modify tumor’s biological behavior through inhibition of EMT, and further reduce the chances of metastasis, that can translate to improved outcome and patient’s survival in advanced disease.