The adult human heart has a limited ability to regenerate after injury, leading to the formation of fibrotic scars and a subsequent loss of function. In fish, mice, and humans, cardiac remodeling after myocardial injury involves the activation of epicardial and endocardial cells, pericytes, stem cells, and fibroblasts. The heart's extracellular matrix (ECM) plays a significant role in the regeneration and recovery process. The epicardium, endocardium, and pericytes reactivate the embryonic program in response to ECM stimulation, which leads to epithelial-mesenchymal transition, cell migration, and differentiation. This review analyzes the role of ECM in guiding the differentiation or dedifferentiation and proliferation of heart components by comparing significant findings in a zebrafish model with those of mammals.