BACKGROUND AND PURPOSE: Significant advancements in therapeutic approaches are imperative to address the prevalent impact of myocardial infarction (MI) on morbidity and mortality rates worldwide. This study explores the therapeutic potential of GATM/Gel hydrogel, focusing on its ability to enhance cardiac repair and functionality after MI through modulation of inflammatory and repair pathways. EXPERIMENTAL APPROACH: The effects of GATM/Gel hydrogel on cardiac recovery were studied in a murine MI model. HA-CHO and gelatin solutions were mixed in situ using a dual syringe with a static mixing needle, and the resulting hydrogel was applied directly to the epicardium during MI modeling, followed by repositioning of the heart and closure of the thorax. Comprehensive in vivo assessments-including echocardiography, electrocardiography, and histopathological analysis-were combined with molecular techniques such as RT-qPCR, Western blotting, and immunofluorescence to elucidate the underlying mechanisms. Key cellular and molecular changes were tracked, focusing on macrophage polarization, angiogenesis, and modulation of the TNF/TNFR2 signaling pathway. KEY RESULTS: Employing the GATM/Gel hydrogel led to a substantial improvement in heart function, shown through enhanced ejection fraction and fractional shortening, and reduced infarction size compared to control groups. Mechanistically, the hydrogel promoted the polarization of anti-inflammatory M2 macrophages and stimulated angiogenesis. Moreover, treatment with GATM/Gel hydrogel altered the TNF/TNFR2 pathway, pivotal in mediating inflammatory responses and facilitating myocardial repair. The discoveries highlight the possibility of GATM/Gel hydrogels as an innovative remedy for MI, providing a twofold role in regulating inflammation and fostering recovery.