Abstract Background The aim of this case is to highlight the importance of strict selection criteria and patient optimization for enhancing outcomes in complex abdominal wall surgery. Methods A fifty-five year-old woman, with a history of diabetes, hypertension, sigmoidectomy and grade IV obesity (BMI 42.8 kg/m2), was counseled for a midline hernia repair (M2–M4, W3). A posterior separation of components with PVDF and PP mesh placement in the retromuscular space was conducted. In the immediate postoperative period, the patient developed respiratory failure, due to abdominal compartment syndrome requiring emergent surgery with mesh removal and an open abdomen treated with Abthera® negative pressure therapy (NPT). After two months in the ICU and NPT without aponeurotic retention, the patient was transferred to our center for definitive treatment. Results The patient arrived with complete abdominal viscera exposure. While a nutritional and respiratory optimization was performed, continuous and progressive dermic traction using a vessel-loop shoelace technique and NPT were applied in order to achieve a progressive abdominal wound closure. Finally, when the skin was sufficient, a new surgery was planned to cover the exposed bowels, where only the cutaneous and subcutaneous planes could be closed. A small dehiscence in the M3 region was treated with skin grafting from the thigh. The patient has since returned home with restored quality of life. Conclusion Inadequate preoperative selection or optimization can lead to life-threatening consequences for the patient. We should promote intensive nutritional education and firmly avoid performing complex abdominal wall procedures in obese patients.