Abstract Atherosclerosis significantly contributes to cardiovascular disease. Traditional treatments for atherosclerosis, such as pharmacological interventions and surgical procedures, have demonstrated limited efficacy and often yield unsatisfactory results. Consequently, safe and effective therapeutic strategies are urgently needed. The atherosclerotic microenvironments, characterized by inflammation driven by foam cells, damaged endothelial cells, recruited leukocytes, lipoproteins, and inflammatory mediators, play a key role in disease progression. By leveraging the biological components and physicochemical properties of these microenvironments, researchers have developed microenvironments‐targeted nanomaterials as a promising approach to treat atherosclerosis. These nanomaterials aim to address and eliminate inflammatory processes. Their functions include repairing endothelial damage, reducing lipoprotein accumulation, inhibiting leukocyte chemotaxis, suppressing foam cell formation, delaying plaque rupture, and preventing thrombosis within the plaque. This review highlights the therapeutic mechanisms and effects of nanomaterials targeting key processes in atherosclerotic microenvironments. Finally, the challenges and prospects of nanomaterial‐based therapies for atherosclerosis are discussed to inspire the development of nanomaterials that modulate atherosclerotic microenvironments, potentially leading to promising clinical applications.