Cardiovascular toxicity associated with anti-tumor therapies is garnering increased attention. Anti-tumor therapies may elevate the risk of acute coronary syndrome, particularly in patients with underlying subclinical atherosclerosis. In this context, a 58-year-old female patient with HER2-positive breast cancer experienced an acute ST-segment elevation myocardial infarction following chemotherapy, dual HER2-targeted therapy, and radiotherapy to the left breast. Prior to the initiation of anti-tumor treatment, chest-computed tomography had identified coronary artery calcification. Angiographic evaluation revealed subtotal occlusion of the middle segment of the left circumflex artery extending to the first obtuse marginal branch, accompanied by multivessel coronary atherosclerotic lesions. Coronary blood flow was restored following emergency interventional treatment. This case indicates that multimodal anti-tumor therapy may facilitate the progression of coronary atherosclerosis, thereby elevating the risk of acute coronary events.