Myocardial infarction with non-obstructive coronary artery (MINOCA) disease represents a heterogeneous clinical conundrum accounting for about 6% of all acute myocardial infarction (MI) cases. Initially believed to be a benign condition, is now becoming clear that MINOCA is associated with a non-negligible risk of mortality, rehospitalization, disability and angina burden at follow-up, with high socioeconomic costs. To date, there are no prospective clinical trials in this population and cannot be assumed that benefits observed in patients suffering from MI with obstructive coronary artery disease may successfully translate to this syndrome. Herein, we comment on the importance of the multimodality assessment to properly identify and treat the specific causes of MINOCA, in order to improve prognosis and the quality of life in these patients.