Immune checkpoint inhibitors (ICIs) are monoclonal antibodies targeting immune checkpoints to enhance anti-tumor responses. Approved ICIs like CTLA-4, PD-1, PD-L1, and LAG-3 have improved cancer outcomes but cause immune-related adverse events (irAEs), including cardiovascular issues such as myocarditis, atherosclerosis, and pericarditis. These irAEs are serious and can be fatal. ICIs like nivolumab and ipilimumab are effective but associated with significant toxicity. New targets like Tim-3 and TIGIT are being explored for improved efficacy. The mechanisms of approved ICIs involve blocking inhibitory signals to enhance T-cell activity. However, ICIs can also cause autoimmune reactions, leading to severe complications. Myocarditis, a rare but deadly irAE, is linked to ICI therapy, with higher risk in combined therapies. Atherosclerosis is also a concern, as ICIs may accelerate plaque formation. Treatment for these irAEs includes corticosteroids and other immunomodulators, but resuming ICI therapy after myocarditis is risky. Atherosclerosis is a major contributor to cardiovascular disease, and ICIs may exacerbate it by increasing inflammation. Understanding these mechanisms is crucial for managing the risks associated with ICI therapy.Immune checkpoint inhibitors (ICIs) are monoclonal antibodies targeting immune checkpoints to enhance anti-tumor responses. Approved ICIs like CTLA-4, PD-1, PD-L1, and LAG-3 have improved cancer outcomes but cause immune-related adverse events (irAEs), including cardiovascular issues such as myocarditis, atherosclerosis, and pericarditis. These irAEs are serious and can be fatal. ICIs like nivolumab and ipilimumab are effective but associated with significant toxicity. New targets like Tim-3 and TIGIT are being explored for improved efficacy. The mechanisms of approved ICIs involve blocking inhibitory signals to enhance T-cell activity. However, ICIs can also cause autoimmune reactions, leading to severe complications. Myocarditis, a rare but deadly irAE, is linked to ICI therapy, with higher risk in combined therapies. Atherosclerosis is also a concern, as ICIs may accelerate plaque formation. Treatment for these irAEs includes corticosteroids and other immunomodulators, but resuming ICI therapy after myocarditis is risky. Atherosclerosis is a major contributor to cardiovascular disease, and ICIs may exacerbate it by increasing inflammation. Understanding these mechanisms is crucial for managing the risks associated with ICI therapy.