Cocaine-induced lesions may cause extensive destruction of the osteocartilaginous structures of the nose, sinuses and palate, a syndrome called CIMDL (cocaine-induced midline destructive lesion). In such cases, reconstructive procedures of the lost soft and hard tissues may be indicated, such as local flaps, regional flaps, and free revascularised flaps. Also, prosthetic obturators have been suggested to overcome the functional problems related to the tissue loss. However, the majority of publications are related to relatively small defects, whereas articles related to the surgical treatment of large midfacial defects are less frequently reported. The objective of this article is to report the authors' experience concerning a unique case consisting of a complex reconstruction of a severe cranial base, midface, palate, and nose defect following cocaine abuse with four revascularised flaps followed by prosthetic restoration with implant-supported prostheses.