Background <p>Chronic pleural empyema in patients with non-expandable lung represents a major therapeutic challenge, particularly in individuals who are poor surgical candidates. While surgical approaches such as decortication or open window thoracostomy remain standard treatments, minimally invasive strategies are increasingly considered for frail or high-risk patients. Tunneled pleural catheters (TPCs) have emerged as a potential alternative; however, clinical data regarding their efficacy and safety in chronic pleural infection remain limited.</p> Methods <p>We conducted a systematic review of studies evaluating the use of TPCs in the management of chronic pleural infections in non-surgical candidates. A comprehensive search was performed in PubMed and other relevant databases up to March 2025. Studies were included if they reported clinical outcomes of TPCs in empyema or pleural infection. Data were extracted on patient characteristics, success rates, complications, and pleurodesis outcomes.</p> Results <p>A total of eight studies including 1,141 patients were analyzed. TPCs were associated with infection control in the majority of reported cases, with complete or partial resolution rates of up to 100% in selected cohorts. In the largest study, the infection rate associated with TPCs was 4.9%, with an infection-related mortality of 0.29%. Post-infection pleurodesis occurred in more than 60% of patients. Case reports and small series described effective symptom relief and radiological improvement over follow-up periods ranging from weeks to months. In selected cases, intrapleural fibrinolytics were administered safely via TPCs.</p> Conclusions <p>TPCs appear to be a feasible and potentially effective management option for carefully selected patients with chronic pleural infection and non-expandable lung who are unfit for surgery. Their use may facilitate ambulatory care, reduce hospitalization, and support pleural symphysis formation in selected cases. Given the limited and predominantly observational nature of the available evidence, TPCs should be considered as part of an individualized, multidisciplinary treatment approach, and further prospective studies are warranted to better define their role alongside other minimally invasive strategies in inoperable pleural empyema.</p>