Developmental cardiac tissue holds a remarkable capacity to regenerate after injury and consists of regenerative mononuclear and diploid cardiomyocytes (MNDCMs). Upon maturation, MNDCMs become binucleated or polyploid and exit the cell cycle. Interestingly, CM metabolism undergoes a profound shift that coincides with the cessation of regeneration in the postnatal heart. However, whether reprogramming metabolism promotes persistence of regenerative MNDCMs enhancing cardiac function and regeneration after injury is unknown. Here, we identify a novel role for RNA-binding protein LIN28a, a master regulator of cellular metabolism, in cardiac regeneration following injury. LIN28a was found as primarily active during cardiac developmental stages and rapidly decreases after birth. LIN28a reintroduction at P0, P3, P5, and P7 decreased maturation-associated polyploidization, nucleation, and cell size enhancing CM cell cycle activity (Ki67+, pHH3+, and AurB+ cells) in LIN28a transgenic pups compared to WT littermates. Moreover, LIN28a overexpression extended CM cell cycle activity beyond P7 concurrent with increased cardiac function 30 days after apical resection. In the adult heart, LIN28a overexpression attenuated CM apoptosis, enhanced CM cell cycle activity, cardiac function, and survival in mice 12 weeks after myocardial infarction compared to WT littermate controls. Alternatively, LIN28a small molecule inhibitor attenuated the pro-regenerative effects of LIN28a on the heart. Mechanistically, Neonatal rat ventricular myocytes (NRVMs) overexpressing LIN28a showed increased glycolysis, ATP production, and activity of metabolic enzymes compared to control. Collectively, LIN28a reprograms CM metabolism and promotes persistence of regenerative MNDCMs in the injured heart enhancing pro-regenerative processes thereby linking CM metabolism to the regulation of ploidy/nucleation and regeneration in the heart.