Deep neck space infections (DNSIs) present significant clinical challenges due to the complex anatomical architecture of the cervical region and the potential for life-threatening complications. Management is further complicated in patients with comorbidities such as diabetes mellitus and heavy smoking, which impair wound healing. This report describes the management of a large (15 × 15 cm) post-operative cervical wound in a patient with previously undiagnosed diabetes and a history of heavy smoking. Following surgical drainage of a Klebsiella pneumoniae abscess, the wound cavity displayed persistent slough and purulent pooling near the carotid sheath. To avoid the morbidity of repeated surgical debridement in this high-risk zone, Negative Pressure Wound Therapy with Instillation and Dwell time (NPWT-i/d) was utilized. Conclusion: The application of NPWT-i/d over a 9-day period successfully reduced bioburden, promoted rapid granulation, and prevented the need for secondary major surgery. This case supports the safe use of NPWT-i/d as an adjunct in complex head and neck wounds.