Cardiovascular disease (CVD) is still a factor of mortality in the whole world. Through canonical and noncanonical pathways and with different receptors, the Wnt/β-catenin signaling pathway plays an essential role in response to heart injuries. Wnt regulates the mobilization and proliferation of cells in endothelium and epicardium in an infarcted heart. Therefore, with its profibrotic effects as well as its antagonism with other proteins, Wnt/β-catenin signaling pathway leads to beneficial effects on fibrosis and cardiac remodeling in myocardium. In addition, Wnt increases the proliferation and differentiation of cardiac progenitors in an ischemic heart. Complex interactions and dual activity of Wnt, the changes in its expression, and mutations that can change its activity during heart development have an adverse effect on cardiac myocardium after injury. However, targeting the Wnt in myocardium with cellular and molecular pathways can be suggested to improve and repair ischemic heart. Given these challenges, in this review article, we deal with the role of Wnt/β-catenin signaling pathway as well as its interactions with other cells and molecules in an ischemic myocardium.