Purpose <p>The management of hernia in immunocompromised patients remains a distinct surgical challenge, characterized by complex risk profiles, heightened susceptibility to infectious complications, and ambiguous consensus on optimal mesh selection and perioperative protocols. As the prevalence of immunosuppression continues to rise due to increasing organ transplant rates, autoimmune diseases, oncological therapies, and advanced age, understanding the nuances of mesh repair in this population is of paramount importance.</p> Methods <p>This review synthesizes current evidence on the safety, efficacy, and outcomes of hernia mesh repair in immunocompromised adults, traversing mesh materials, infection mitigation strategies, surgical techniques, recurrence and complication rates, patient-reported outcomes, cost-effectiveness, and future research imperatives.</p> Results <p>Advanced mesh materials—particularly long-acting resorbable meshes—show superior long-term durability but at elevated cost. The risk for mesh infection and recurrence is proportionate to immunosuppression burden, comorbidities, and operative field contamination. Notably, modern synthetic meshes, when coupled with stringent perioperative infection control and risk-mitigation strategies, offer durable repair with acceptable safety profiles, even in immunocompromised hosts.</p> Conclusion <p>There is insufficient evidence to support routine use of biologic mesh, except in select contaminated fields. Patient-reported metrics are increasingly recognized as essential for outcome assessment, though standardization remains incomplete. Cost-effectiveness favors synthetics unless contamination risks predominate or patient preference dictates otherwise. Gaps include inconsistent immunocompromised patient definitions, limited long-term data, and lack of tailored guidelines. Prospective, multicenter studies integrating real-world patient-reported and economic data are needed.</p>