Wound care management represents a substantial economic burden, with costs in the United States exceeding $150 billion annually. Negative pressure wound therapy (NPWT) has emerged as an effective adjunct for complex, acute, chronic, and surgical wounds, demonstrating improvements in healing, perfusion, and complication reduction. However, the high cost of NPWT relative to standard dressings necessitates evaluation of its cost-effectiveness. This review synthesizes key evidence across wound types and clinical contexts, highlighting that NPWT can be cost-effective, particularly when applied early and in high-risk or complex wounds, though results vary by etiology, patient factors, device type, and healthcare system. Closed-incision NPWT shows potential for preventing surgical site infections and reducing hospital costs in selected populations. In contrast, in certain indications, such as open lower limb fractures or low-risk surgical procedures, cost-effectiveness remains uncertain. Tailored, risk-based use of NPWT, as well as exploration of lower-cost alternatives and system-specific strategies, will be critical to optimize both clinical and economic outcomes.