Myocardial infarction with non-obstructive coronary artery (MINOCA) is a condition previously thought to be benign but has recently been shown to have comparable mortality to that of acute coronary syndrome with obstructive coronary disease. The heterogeneity of the underlying aetiology makes the assessment, investigation and treatment of patients with MINOCA challenging. The majority of patients with MINOCA presenting with ST-segment elevation myocardial infarction (STEMI) generally have an underlying coronary or myocardial cause, predominantly plaque disruption or myocarditis. In order to make the correct diagnosis, including the cause of the presentation, a meticulous and methodical approach is required, with targeted investigations. Stratification of patients to guide investigations that are more likely to provide the diagnosis will allow correct treatment to be initiated promptly. Herein, we review the contemporary incidence, aetiology, recommended assessment and treatment of patients with MINOCA presenting with STEMI.