Lipoprotein(a) (Lp(a)) is an established independent risk factor for atherosclerotic cardiovascular disease, particularly in the development of high-risk coronary plaques (HRPs). Elevated Lp(a) contributes to lipid accumulation, vascular inflammation, and plaque instability, primarily through oxidized phospholipids that promote monocyte adhesion and foam cell formation. Genetic studies have identified variants in the LPA gene as major determinants of Lp(a) levels, with higher concentrations consistently associated with adverse cardiovascular outcomes. Intravascular imaging techniques, such as optical coherence tomography and intravascular ultrasound, along with coronary computed tomography angiography (CCTA), have confirmed strong correlations between elevated Lp(a) and increased plaque burden, lipid-rich necrotic cores, and thin fibrous caps. In addition to coronary involvement, Lp(a) is implicated in systemic atherosclerosis, contributing to peripheral artery disease, cerebrovascular disease, and calcific aortic stenosis. Although conventional lipid-lowering therapies exert minimal effects on Lp(a), novel treatments such as proprotein convertase subtilisin/kexin type 9 inhibitors and RNA-targeted agents offer promising approaches to mitigating Lp(a)-mediated risk. This review summarizes current insights into the pathophysiological role of Lp(a) in HRP formation and progression, integrating evidence from genetic, mechanistic, and imaging studies, while highlighting emerging therapeutic strategies. Nonetheless, continued research is essential to enhance our understanding of Lp(a)-driven plaque vulnerability and to inform precision-targeted cardiovascular prevention.