The recently introduced concept of 'exposome' emphasizes the impact of non-traditional threats onto cardiovascular health. Among these, air pollutants – particularly fine particulate matter < 2.5 μm (PM2.5) – have emerged as significant environmental risk factors for cardiovascular disease and mortality. PM2.5 exposure has been shown to induce endothelial dysfunction, chronic low-grade inflammation, and cardiometabolic impairment, contributing to the development and destabilization of atherosclerotic plaques. Both short- and long-term exposure to air pollution considerably increase the incidence of ischemic heart disease (IHD)-related events, with clinical evidence linking pollution to higher mortality and adverse prognosis, especially in vulnerable populations. In this review, we explore the mechanistic pathways through which air pollutants exacerbate atherosclerotic cardiovascular disease (ASCVD) and discuss their clinical impact.