Abstract: The clinical efficacy of therapeutic drugs for cardiovascular diseases was severely limited by the nonspecific distribution of the drugs. The present review systematically summarized cardiac-targeted drug delivery systems, focusing on intelligent design strategies that mimicked endogenous cardiac repair pathways, recognized myocardial biomarkers, leveraged the EPR effect of lesion vessels, and responded to the unique microenvironment of lesions. Moreover, the review discussed local drug administration methods and combinative strategies of various cardiac targeting to promote concentrated drug delivery at cardiac lesion sites across physiological barriers. Accordingly, the present review provided an in-depth analysis of the challenges faced by cardiac-targeted delivery systems and looked forward to their clinical transformation prospects. Reviewing the intelligent design and application prospects of cardiac-targeted strategies aimed to provide important references for the research and development of cardiac-targeted drug delivery.