Background <p>Infectious endophthalmitis following penetrating ocular trauma represents an acute and often blinding disease with a generally poor prognosis. The causative pathogens involved are diverse, among which bacterial organisms are the most prevalent. In contrast, infections caused by fungi of the order Mucorales are rare, constituting acute and fulminant opportunistic mycoses. These fungal infections are characterized by an insidious onset and are associated with an exceedingly high mortality rate, particularly in patients with comorbid diabetes mellitus.</p> Case presentation <p>A 60-year-old diabetic male presented with severe, rapidly progressive infectious endophthalmitis after a penetrating ocular injury. Imaging demonstrated substantial destruction of the right eyeball and its adnexa, as well as bony absorption of the medial orbital wall. Intraoperative tissue specimens on day 3 of admission were cultured for <i>Rhizopus arrhizus</i>, <i>Pseudomonas aeruginosa</i>, <i>Enterococcus faecalis</i>. The treatment regimen was guided by pathogen identification and drug susceptibility results. It consisted of systemic intravenous liposomal amphotericin B (L-AmB) and piperacillin-tazobactam, aggressive blood glucose management, topical medication, and two sessions of surgical debridement. By day 28 of admission, the patient was discharged with good recovery, Outpatient follow-up at 10 and 40 days after discharge showed no abnormalities and the prognosis was good.</p> Conclusions <p>Early targeted Sanger sequencing identification and multimodal therapy—combining antifungal, antibacterial, and surgical interventions—were critical to overcoming the diagnostic challenges and therapeutic complexities in this immunocompromised host.</p>