Mesh infection is a significant complication after hernia surgery and is associated with increased morbidity, reoperation rates, and impaired quality of life. Risk factors include chronic obstructive pulmonary disease (COPD), obesity, diabetes, smoking, and advanced age. We present a 49-year-old obese woman with poorly controlled type 2 diabetes mellitus and multiple significant comorbidities, including congestive heart failure, permanent atrial fibrillation, chronic kidney disease, dyslipidemia, gout, bronchiectasis, and a history of multiple abdominal surgeries, who developed a postoperative mesh infection following onlay hernioplasty. Wound cultures revealed Pseudomonas aeruginosa with specific antibiotic sensitivities. Management involved mesh removal, extensive debridement, targeted antibiotic therapy, and vacuum-assisted closure (VAC) therapy followed by abdominoplasty, which led to complete wound healing. Despite successful infection management, the patient developed a recurrent hernia during follow-up. This case demonstrates the effectiveness of VAC therapy in managing infected mesh sites after hernia repair while highlighting the challenge of maintaining long-term hernia repair integrity following mesh removal. The case underscores the importance of balancing infection control with structural support in high-risk patients with multiple significant comorbidities.