Abstract Myocardial ischemia–reperfusion (I/R) injury is a multifaceted process observed in patients with coronary artery disease when blood flow is restored to the heart tissue following ischemia-induced damage. Cardiomyocyte cell death, particularly through apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis, is pivotal in myocardial I/R injury. Preventing cell death during the process of I/R is vital for improving ischemic cardiomyopathy. These multiple forms of cell death can occur simultaneously, interact with each other, and contribute to the complexity of myocardial I/R injury. In this review, we aim to provide a comprehensive summary of the key molecular mechanisms and regulatory patterns involved in these five types of cell death in myocardial I/R injury. We will also discuss the crosstalk and intricate interactions among these mechanisms, highlighting the interplay between different types of cell death. Furthermore, we will explore specific molecules or targets that participate in different cell death pathways and elucidate their mechanisms of action. It is important to note that manipulating the molecules or targets involved in distinct cell death processes may have a significant impact on reducing myocardial I/R injury. By enhancing researchers’ understanding of the mechanisms and interactions among different types of cell death in myocardial I/R injury, this review aims to pave the way for the development of novel interventions for cardio-protection in patients affected by myocardial I/R injury.