The transcription factor zinc finger E-box binding homeobox 1 (ZEB1) is a critical inducer of epithelial mesenchymal transformation (EMT) and plays a robust role in tumor metastasis. It can promote not only the movement and diffusion of tumor cells but also cell stemness, treatment resistance, tumor metastasis and immune escape. The expression of ZEB1 is strictly regulated by a variety of pretranscriptional and posttranscriptional signaling pathways and molecules. Increasing evidence indicates that protein modifications such as methylation and acetylation of ZEB1 can also affect tumor metastasis. More importantly, ZEB1 induces immunosuppressive cells and chemokines into the tumor microenvironment (TME), leading to the formation of a tumor immunosuppressive microenvironment. This review summarizes the regulatory factors involved in ZEB1 expression and its important role. The areas of research covered in this review contribute to providing new thoughts and new treatment insights for targeted ZEB1 therapy of malignant tumors.