Nontuberculous mycobacteria (NTM) skin infections remain therapeutically challenging. Given the diversity in infections, host responses, and antimicrobials, clinical guidelines are often built on case series and observational studies. In this commentary, we respond to a paper by Stemkens et al. that introduces an emerging strategy: adjunctive negative pressure wound therapy with instillation and dwell time combined with topical antibiotics for refractory NTM skin and soft tissue infections. We delve into the primary considerations surrounding this innovative approach.