Hormone therapy with anti-estrogenic purposes is a cornerstone in breast cancer therapy that expresses estrogen receptors, the most frequent immunohistotype among invasive breast cancer. Hormone therapy is administered for a long time and affects the cardio-metabolic profile with possible interactions with the woman's intrinsic cardiovascular risk and the cardiotoxic effects of other treatments (chemotherapy, radiotherapy, target therapy). In this review, we analyze the pathophysiological implications and cardiovascular effects of hormone therapy providing useful elements for the creation of a personalized management program based on the "stepwise approach" as recommended by the 2021 cardiovascular disease prevention guidelines of the European Society of Cardiology and on the possible use of new antidiabetic drugs potentially useful for the management of the metabolic syndrome.