M1 macrophages polarization has been reported as the direct risk of acute myocardial infarction (AMI) occurrence and worsen AMI prognosis, especially for hyperinflammation-associated AMI. However, clinic treatments remain challenges, including off-target and side-effects. The development of enzyme mimetics could provide effective treatments for a wide variety of diseases. Herein, nanomaterials were used to create artificial hybrid nanozymes. In this study, we synthesized in situ zeolitic imidazolate framework nanozyme (ZIF-8zyme) with anti-oxidative and anti-inflammatory ability to repair microenvironment via reprogramming M1 macrophages polarization. In vitro study reported that a metabolic reprogramming strategy that the improvement of glucose import and glycolysis with ZIF-8zyme via inhibiting ROS levels led to a metabolic crisis within the macrophages. ZIF-8zyme shifted the polarization of M1 macrophages toward higher production of M2 phenotype, decreased proinflammatory cytokines secretion, and promoted significant survival of cardiomyocytes under hyperinflammation condition. Moreover, ZIF-8zyme elicits more potent macrophages-polarizing effects under hyperinflammation condition. Therefore, metabolic reprogramming strategy based on ZIF-8zyme is a promising AMI therapy, especially for hyperinflammation-associated AMI.Copyright © 2023. Published by Elsevier B.V.