Atherosclerosis is one of the leading causes of vascular diseases, with high morbidity and mortality worldwide. Macrophages play a critical role in the development and local inflammatory responses of atherosclerosis, contributing to plaque rupture and thrombosis. Considering their central roles, macrophages have gained considerable attention as a therapeutic target to attenuate atherosclerotic progression and stabilize existing plaques. Nanoparticle-based delivery systems further provide possibilities to selectively and effectively deliver therapeutic agents into intraplaque macrophages. Although challenges are numerous and clinical application is still distant, the design and development of macrophage-targeting nanoparticles will generate new knowledge and experiences to improve therapeutic outcomes and minimize toxicity. Hence, the review aims to discuss various strategies for macrophage modulation and the development and evaluation of macrophage targeting nanomedicines for anti-atherosclerosis.