<p>Mucormycosis, a severe fungal infection with high morbidity and mortality rates, particularly affects immunocompromised individuals. Standard treatments involving debridement and systemic antifungals often encounter resistance, especially in cutaneous forms due to systemic toxicity and poor tissue penetration of Amphotericin B. This case series investigates the effectiveness of intralesional Amphotericin B for targeted delivery with minimal systemic side effects. Three cases are presented: a 50-year-old man with invasive mucormycosis in the sinuses and frontal bone, a 10-year-old boy with poorly controlled diabetes and periorbital mucormycosis, and a 62-year-old man with diabetes and periorbital cellulitis from invasive fungal sinusitis. All underwent surgical debridement followed by systemic and intralesional Amphotericin B. The intralesional treatment, administered over seven consecutive days, resulted in significant clinical and radiological improvements, with complete resolution of cutaneous involvement. This series marks the first documentation of intralesional Amphotericin B’s efficacy in mucormycosis, suggesting it as a promising alternative for refractory cases. Previous studies on cutaneous leishmaniasis also support its potential, showing high recovery rates with minimal side effects. Further research is needed to confirm these findings and optimize treatment protocols.</p>