The management of severe burns is a complex process that requires a multidimensional approach to ensure optimal healing of burn wounds, minimize complications, and improve the prognosis of patients. Surgical debridement is considered the gold standard for removing necrotic tissue; however, this approach involves risks such as bleeding, the potential removal of viable tissue during excision, and technical challenges in complex anatomical areas. Recent advancements highlight the role of enzymatic debridement using NexoBrid®, which offers a less invasive alternative to surgical excision while having the ability to selectively debride necrotic tissue and preserve viable tissue. NexoBrid® has shown efficacy in reducing debridement time, minimizing the need for additional surgeries, and improving overall wound healing outcomes. This review discusses the clinical indications, advantages, and considerations for choosing between surgical and enzymatic debridement. Emerging studies suggest the potential for enzymatic debridement to be safe and effective even for larger burn areas, making it a promising option in modern burn care. However, ongoing evaluation and integration into clinical protocols will be essential to fully realize its benefits in specialized burn treatment and to establish protocols.