The inflammatory response following myocardial infarction is crucial for cardiac repair but can also lead to post-infarction remodeling and heart failure. The initial inflammatory phase involves the activation of toll-like receptors, complement system, and reactive oxygen species, which trigger the upregulation of cytokines and chemokines. Leukocytes are recruited to remove dead cells and matrix debris, while myofibroblasts secrete matrix proteins to form a scar. Timely repression of inflammation is essential for effective healing, followed by the activation of myofibroblasts. Members of the transforming growth factor-β (TGF-β) family play a critical role in suppressing inflammation and activating a pro-fibrotic program. Understanding the complex pathophysiology of post-infarction remodeling is crucial for developing targeted therapies. Biomarker-based approaches are needed to identify patients with distinct pathophysiologic responses and to implement inflammation-modulating strategies effectively.The inflammatory response following myocardial infarction is crucial for cardiac repair but can also lead to post-infarction remodeling and heart failure. The initial inflammatory phase involves the activation of toll-like receptors, complement system, and reactive oxygen species, which trigger the upregulation of cytokines and chemokines. Leukocytes are recruited to remove dead cells and matrix debris, while myofibroblasts secrete matrix proteins to form a scar. Timely repression of inflammation is essential for effective healing, followed by the activation of myofibroblasts. Members of the transforming growth factor-β (TGF-β) family play a critical role in suppressing inflammation and activating a pro-fibrotic program. Understanding the complex pathophysiology of post-infarction remodeling is crucial for developing targeted therapies. Biomarker-based approaches are needed to identify patients with distinct pathophysiologic responses and to implement inflammation-modulating strategies effectively.