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Cardiovascular diseases are the main cause of death worldwide, a trend that will continue to grow over the next decade. The heart consists of a complex cellular network based mainly on cardiomyocytes, but also on endothelial cells, smooth muscle cells, fibroblasts, and pericytes, which closely communicate through paracrine factors and direct contact. These interactions serve as valuable targets in understanding the phenomenon of heart remodeling and regeneration. The advances in nanomedicine in the controlled delivery of active pharmacological agents are remarkable and may provide substantial contribution to the treatment of heart diseases. This review aims to summarize the main mechanisms involved in cardiac remodeling and regeneration and how they have been applied in nanomedicine.