Cardiovascular diseases (CVDs), including ischemic heart disease, stroke, hypertensive heart disease, and peripheral arterial disease, are the leading causes of global morbidity, disability, and mortality, posing threats to human life and health [1]. Although cardiovascular health can be effectively promoted by controlling interfering risk factors, these influences are often not easily perceived and are cumulative over time. By the time symptoms manifest, such measures may no longer be effective to prevent disease onset. Therefore, new therapeutic strategies are needed to decelerate CVD progression and improve its long-term prognosis. Immunological responses are considered the most prevalent mechanism of cardiovascular pathogenesis, and secreted immune metabolites are essential for immune cell effector functions and important components of cell–cell communication networks [2], [3]. Itaconate is a secondary metabolite of the tricarboxylic acid (TCA) cycle and a key hub metabolite that links immune and metabolic functions. Itaconate modulates metabolic levels by inducing the activation of nuclear factor erythroid 2-related factor 2 (NRF2) through the alkylation of Kelch-like ECH-associated protein 1 (KEAP1) and by inhibiting succinate dehydrogenase, which regulates glycolysis and oxidative stress. It also regulates inflammatory and interferon responses by modulating NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammatory vesicles, the Ten-Eleven Translocation-2 (TET2) enzyme, and the stimulator of interferon gene (STING)–interferon (IFN) axis. These signaling pathways participate in a range of pathophysiological processes, including the maintenance of cardiovascular homeostasis. This article reviews the properties of itaconate and highlights its mechanisms, functional roles, and the available evidence for its role as a target for cardioprotection through immune modulation.