Percutaneous non-valvular structural interventions, encompassing patent foramen ovale, atrial or ventricular septal defect closure and left atrial appendage closure, are usually performed in young and healthy patients and represent a valid alternative to pharmacological or surgical interventions. In order to minimize procedural and device related complications, a careful pre-procedural planning together with an accurate intra-procedural imaging are crucial to improve patient's outcome. In this article, we review currently available evidence on patient selection, procedural planning and interventional guidance helping physician to determine who will derive the most benefit from the procedure.