Acute myocardial infarction (AMI) is an acute ischemic heart disease, which can be attributed to a plaque rupture and acute thrombosis of coronary atherosclerotic lesions. Despite decreased acute mortality for AMI with the widespread use of percutaneous coronary intervention (PCI) in japan, an increase in patients with chronic heart failure following cardiac ischemia-reperfusion injury has become a crucial issue. Therefore, preventing the progression of AMI to chronic heart failure is a significant unmet medical need in cardiovascular diseases. In this review, together with our previous work, we will highlight recent advances in the development of nanotechnology-based drug delivery system (DDS) for the treatment of AMI, and discuss their therapeutic potential for clinical applications.