Cancer and cardiovascular disease remain the leading causes of morbidity and mortality worldwide, and the two separate disease entities share several similarities and possible interactions. Patients with cancer may have underlying cardiovascular disease, which is often exacerbated by the stress of tumor growth or treatment. At the same time, cardiotoxicity induced by anti-cancer therapies or the malignant process itself can lead to new cardiovascular diseases. Efforts have been made to find a rational explanation for this phenomenon. As a classical tumor-promoting factor, we notice that SNAI2 simultaneously plays an important pathogenic role in cardiovascular diseases. Moreover, there are several striking parallels in the mechanisms of cancer and CVD, such as shared risk factors (e.g., smoking and diabetes), cellular phenotypic switching, and metabolic remodeling, all of which are mediated by SNAI2. This review aims to summarize SNAI2's role in the core mechanisms linking cancer and CVD, as well as explore therapeutic approaches targeting SNAI2 and also seeks to provide insights into the common mechanisms underlying both cancer and CVD.© 2025 Federation of American Societies for Experimental Biology.