This narrative review provides a comprehensive analysis of the molecular biomarkers associated with symptomatic carotid plaques and their role in plaque vulnerability. Vulnerable carotid plaques, characterized by features such as microcalcification, neovascularization, lipid-rich necrotic cores, intraplaque hemorrhage, thin fibrous caps, and plaque surface ulceration, are crucial in understanding the pathophysiology of ischemic stroke. Inflammatory biomarkers, lipid-related markers, and proteolytic enzymes are key molecules that contribute to plaque instability. Proteomic studies have revealed complex molecular alterations, including dysregulation of extracellular matrix remodeling proteins, inflammatory mediators, and lipid metabolism-related proteins. Macrophage polarization, particularly from M1 to M2 phenotypes, plays a significant role in plaque vulnerability. Other molecules, such as osteopontin and CD40-CD40L signaling, also contribute to plaque instability. The rupture of vulnerable plaques is influenced by local dynamic forces and extrinsic factors, leading to endothelial damage and thrombosis. Microembolism from carotid plaques is another mechanism responsible for cerebral ischemia, with specific biomarkers associated with increased risk. Fibrous cap thickness is a critical factor in plaque stability, and thin-cap atheroma is a strong predictor of plaque rupture. The review highlights the importance of these molecular pathways in the development of ischemic stroke and provides insights into potential therapeutic targets.This narrative review provides a comprehensive analysis of the molecular biomarkers associated with symptomatic carotid plaques and their role in plaque vulnerability. Vulnerable carotid plaques, characterized by features such as microcalcification, neovascularization, lipid-rich necrotic cores, intraplaque hemorrhage, thin fibrous caps, and plaque surface ulceration, are crucial in understanding the pathophysiology of ischemic stroke. Inflammatory biomarkers, lipid-related markers, and proteolytic enzymes are key molecules that contribute to plaque instability. Proteomic studies have revealed complex molecular alterations, including dysregulation of extracellular matrix remodeling proteins, inflammatory mediators, and lipid metabolism-related proteins. Macrophage polarization, particularly from M1 to M2 phenotypes, plays a significant role in plaque vulnerability. Other molecules, such as osteopontin and CD40-CD40L signaling, also contribute to plaque instability. The rupture of vulnerable plaques is influenced by local dynamic forces and extrinsic factors, leading to endothelial damage and thrombosis. Microembolism from carotid plaques is another mechanism responsible for cerebral ischemia, with specific biomarkers associated with increased risk. Fibrous cap thickness is a critical factor in plaque stability, and thin-cap atheroma is a strong predictor of plaque rupture. The review highlights the importance of these molecular pathways in the development of ischemic stroke and provides insights into potential therapeutic targets.