Stenotrophomonas maltophilia is characterised by intrinsic multidrug resistance, posing therapeutic challenges. Although pathogen prevalence varies between cohorts, Staphylococcus aureus and Enterococcus faecium are frequently identified as leading causes of diabetic foot osteomyelitis, whereas infections due to S maltophilia are rare. We present the case of a 64-year-old Puerto Rican woman with type 2 diabetes and peripheral neuropathy, who developed a chronic ulcer in the left lateral malleolus following an untreated ankle fracture. CT revealed substantial bony destruction suggestive of osteomyelitis. Deep wound cultures revealed co-infection with S maltophilia and extended-spectrum β-lactamase (ESBL)-producing Escherichia coli , which are both resistant to multiple standard treatments. Despite aggressive antibiotic therapy, a follow-up MRI scan confirmed extensive osteonecrosis. The patient ultimately required a below-knee amputation. This case highlights the clinical impact of S maltophilia in diabetic foot infections, particularly its association with increased risk of major amputation. The co-isolation of ESBL-producing E coli further complicated management and likely contributed to the poor outcome.