A 64-year-old man underwent piecemeal EMR of a 20-mm duodenal adenoma and developed delayed perforation with retroperitoneal free air. Endoscopy revealed a large duodenal wall defect. ERCP with biliary and pancreatic stenting was performed to divert secretions. The defect was treated with enteral self-expandable metal stents and continuous negative-pressure therapy using double-lumen tubes, combined with periduodenal drainage and enteral nutrition. Despite initial improvement, stent migration and infected retroperitoneal collection occurred. A step-up hybrid approach including deployment of a customized chimeric duodenal stent and combined endoscopic–percutaneous drainage achieved complete sealing of the defect and fistula. Follow-up imaging confirmed resolution of the collection. The patient resumed oral feeding and was discharged in good clinical condition.