Background: Lymphatic leaks are well-known complications of major thoracic or abdominal surgeries, which significantly heighten morbidity and mortality rates. While the existing literature provides insights into managing these post-operative leaks, with a step-up approach from conservative measures (CMs) to surgical intervention, there are no standardized treatment guidelines. The purpose of this paper is to offer a management algorithm of post-operative lymphatic leaks based on a systematic literature review (SLR) of the therapeutic effect of Lipiodol lymphangiography (LL), completed by a case series of five patients who underwent LL in our department. Methods: In this IRB-approved study, we conducted an SLR following the PRISMA guidelines, using a PICOS. A quality assessment was performed for each study. The case series consisted of consecutive patients who underwent LL for diagnostic and therapeutic purposes at our institution between September 2018 and December 2020. Results: A total of 39 observational studies were included in the SLR comprising 11 retrospective case reviews (Group 1), and 3 case series as well as 25 case reports (Group 2). In total, these studies report cases of 557 patients (51.52% presenting oncological diagnoses; 43.98% having benefited from lymphadenectomy). Lymphatic or chylous fistulas were the most encountered complication, followed by chylothorax. The median volume of Lipiodol injected during lymphography was 11.7 mL (range: 9.8–75 mL). Overall, LL was technically successful in 77.7% (366/471) of patients. The clinical success of all technically successful LLs was 80.6% (295/366). Time-to-leak resolution after lymphography varied between 1 and 31 days. The factors associated with treatment failure were a high leak output (>500 mL/day) and Lipiodol extravasation on post-LL imaging. Our case series consisted of five patients (mean age: 62 ± 9.24 years; 20% female; 100% oncological diagnoses; 60% having beneficiated from lymphadenectomy). Technical and clinical successes were 80% (4/5) and 75% (3/4), respectively. Time-to-leak resolution varied between 1 and 4 days. The volume and technique of LL was not different from that identified in the SLR. Conclusions: LL is a safe procedure with high technical and clinical success rates that could be proposed as both a diagnostic and therapeutic solution for patients with post-operative central lymphatic lesions.