Post-myocardial infarction (MI) ventricular septal defects (VSD) are a rare but life-threatening complication of acute MI, with very high mortality rates even if timely approached by surgical repair. Transcatheter closure is an attractive alternative to surgery. However, this option is currently deemed challenging and often unsuitable in complex VSD. We report the case of a young woman in poor hemodynamic conditions due to a complex post-MI VSD. A two-step percutaneous VSD closure was successfully performed adopting a patient-tailored approach based on a throughout knowledge of the anatomic and functional picture using both commercially available dedicated and off-label devices.