Abstract: The development of immune checkpoint inhibitors (ICI) has revolutionized cancer treatment. ICI stimulates the immune system to recognize and destroys cancer cells via immune checkpoint proteins. However, these drugs can also induce immune-related adverse events (irAE) in off-target organs, such as the heart. The most common manifestation of heart damage is myocarditis, and these rear off-target effects can be life-threatening. Existing data indicate that ICI induces miss-target effects through several mechanisms, including direct binding to surface proteins expressed in normal tissues, activation of T cells that cross-react with miss-target tissues, production of autoantibodies and pro-inflammatory cytokines. A better understanding of the adverse effects of cancer immunotherapy and its underlying mechanisms will help to develop biomarkers to identify at-risk patients and prevent these irAEs.