Atherosclerosis is considered one of the primary causes of cardiovascular diseases (CVDs). Unpredictable rupture of the vulnerable atherosclerotic plaques triggers adverse cardiovascular events such as acute myocardial syndrome and even sudden cardiac death. Therefore, assessing the vulnerability of atherosclerotic plaques and early intervention are of significance in reducing CVD mortality. Nanomedicine possesses tremendous advantages in achieving the integration of the diagnosis and therapy of atherosclerotic plaques because of its magnetic, optical, thermal, and catalytic properties. Based on the pathological characteristics of vulnerable plaques, stimuli-responsive nanoplatforms and surface-functionalized nanoagents are designed and have drawn great attention for accomplishing the precise imaging and treatment of vulnerable atherosclerotic plaques due to their superior properties, such as high bioavailability, lesion-targeting specificity, on-demand cargo release, and low off-target damage. Here, the characteristics of vulnerable plaques are generalized, and some targeted strategies for boosting the accuracy of plaque vulnerability evaluation by imaging and the efficacy of plaque stabilization therapy (including antioxidant therapy, macrophage depletion therapy, regulation of lipid metabolism therapy, anti-inflammation therapy, etc.) are systematically summarized. In addition, existing challenges and prospects in this field are discussed, and it is believed to provide new thinking for the diagnosis and treatment of CVDs in the near future.