Atherosclerosis (AS), the leading cause of cardiovascular diseases, demands innovative translational approaches. This review critically examines the dual role of extracellular vesicles (EVs) as key pathological mediators and emerging clinical tools in AS, while acknowledging current limitations in clinical validation, standardization challenges, and regulatory pathways. We systematically analyze how EVs dynamically regulate disease progression across all stages from endothelial dysfunction to plaque rupture by delivering specific biomolecules (e.g., miRNAs, cytokines, proteins, lipids) that modulate endothelial integrity, foam cell formation, and vascular smooth muscle cell phenotype. Critically, we distinguish between established mechanistic insights and preliminary translational findings, highlighting gaps between preclinical promise and clinical reality. We evaluate circulating EVs as potential non-invasive diagnostic and prognostic biomarkers—emphasizing the need for standardized pre-analytical protocols and large-scale prospective validation—and assess engineered EVs as novel targeted therapeutic delivery vehicles, addressing manufacturing scalability, off-target effects, and immunogenicity concerns. By integrating pathophysiological mechanisms with diagnostic and therapeutic applications, this review provides a realistic translational roadmap, positioning EVs at the forefront of advancing precision medicine in atherosclerosis management, while outlining critical milestones required for clinical implementation.