This paper describes the holistic management and contribution of critical care to the successful treatment of the life-threatening condition, Fournier’s gangrene, in patients prescribed sodium-glucose co-transporter-2 (SGLT2) inhibitors, using a case report for illustration. A gentleman in his 70s, prescribed empagliflozin, an SGLT2 inhibitor for managing his diabetes and heart failure, presented in a moribund state to the Emergency Department. The interplay of his comorbidities and medication regimen created a scenario that heightened his risk of developing the life threatening condition of Fournier’s gangrene, which was successfully managed. We highlight several critical considerations for a favorable outcome in the setting of critical care. A comprehensive system approach with awareness of the risks associated with SGLT2 inhibitor therapy is crucial to effectively managing Fournier’s gangrene in critical care.