Our experimental results indicate that cardiac exosomes secreted from post-MI hearts play an essential role in desensitizing cancer cells to ferroptotic death thereby promoting tumor growth, and exosomal miR-22-3p secreted from cardiomyocytes critically downregulates the expression of acyl-CoA synthetase long-chain family member 4 (ACSL4) as a molecular mechanism for the suppression of ferroptosis susceptibility in cancer cells in vivo and in vitro. Here, ACSL4 is linked to myocardial infarction.