Atherosclerosis is the elemental precondition for any cardiovascular disease and the predominant cause of ischemic heart disease that often leads to myocardial infarction. The systemic risk factors play an important role in the starting and progression of atherosclerosis. The multifactorial origin causes the complexity of disease. Beside the traditional risk factors, genetic predisposition is a strong risk factor. Many studies have intensively researched cardioprotective drugs, which can relieve myocardial ischemia and reperfusion injury, thereby reducing infarct size. A better understanding of abnormal epigenetic pathways in the myocardial pathology, may result in new treatment options. The individualized therapy based on genome sequencing is important for an effective future medical treatment. Studies based on multiomics help to better understand the pathophysiological mechanism of several diseases at a molecular level. Epigenomic, transcriptomic, proteomic and metabolomic researches might be essential in detecting the pathological phenotype of myocardial ischemia and ischemic heart failure.