Chronic and nonhealing wounds represent a major clinical and economic burden, particularly in patients with complex comorbidities such as diabetes, vascular disease, and autoimmune disorders. Conventional wound care alone is often insufficient in these cases, driving the development and adoption of adjunctive therapies that enhance the body’s intrinsic healing mechanisms. This chapter reviews key adjunctive modalities used in complex wound management, focusing on their mechanisms, clinical applications, and emerging evidence. Negative pressure wound therapy (NPWT) has become a mainstay in the treatment of acute and chronic wounds, improving drainage, reducing bacterial burden, enhancing perfusion, and stimulating granulation tissue formation, with demonstrated benefits in wound closure rates, infection control, and cost-effectiveness. Extracorporeal shock wave therapy (ESWT), as a form of mechanotherapy, promotes angiogenesis, modulates fibroblast activity, remodels extracellular matrix, and shows promise in refractory wounds and scar management. Oxygen therapy interventions, including hyperbaric oxygen therapy (HBOT) and topical oxygen therapy (TOT), improve tissue oxygenation, support collagen synthesis and angiogenesis, and reduce infection in difficult-to-heal ulcers and burns. Additional adjunctive options such as recombinant growth factors, stem cell therapies (including MSC- and ASC-based approaches), electrical stimulation, and photobiomodulation therapy(PBMT) are discussed, alongside bioengineered scaffolds, skin substitutes, and nanotechnology-enabled delivery systems that further optimize the wound microenvironment. The chapter also addresses practical challenges, including high costs, limited reimbursement, stringent regulatory frameworks, the need for careful patient selection, and adherence to often intensive treatment protocols. Finally, we highlight future directions, such as portable devices, combined-therapy strategies, and the integration of artificial intelligence for personalized treatment planning and outcome prediction. Collectively, these adjunctive therapies are reshaping modern wound care and hold substantial potential to improve outcomes in patients with the most challenging wounds