Atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction and ischemic stroke, is a leading cause of death and disability worldwide and is expected to rise further by 2030. Once limited to industrialized nations, atherosclerosis has become a global issue due to the epidemiological transition from infectious to chronic metabolic diseases. Lipoproteins (chylomicrons, VLDL, LDL, HDL) and apolipoproteins play key roles in lipid metabolism and atherosclerosis development. Macrophages in plaques influence inflammation and plaque stability, with iron homeostasis also impacting disease progression. Therapies include personalized diets, statins, niacin, omega-3s, fibrates, and antiplatelet agents. Innovative strategies involve natural products and nanotechnology for targeted drug delivery, especially to macrophages and the endothelium, reducing systemic side effects. In summary, advancing therapies based on molecular insights and patient-specific factors are essential to combat this widespread chronic disease.