The extra-pleural pneumonectomy (EPP) is a standardised surgical procedure born for pleural tuberculosis and later used in pleural cancer treatment, especially in malignant pleural mesothelioma (MPM). This systematic review aimed to focus on the actual overall EPP role in surgical oncology. The literature search was performed from January 1985 to January 2018 In PubMed, Embase, and Cochrane according to PRISMA protocol. The search was restricted to publications in English with the research words “extrapleural pneumonectomy”, “malignant pleural mesothelioma”, “pleural malignancies”. The results were then filtered focusing only on papers with series of patients treated with EPP, for mesothelioma and non-mesothelioma malignancies. The search was restricted to publications in English. We found a 5-year overall survival (OS) ranging from 0 to 78%. The peri-operative mortality and morbidity ranged from 0 to 11.8% and 0 to 82.6%, respectively. The most represented and described post-operative complications reported were ARDS, pericardial tamponade, cardiac herniation, pulmonary embolism, respiratory infections, respiratory failure, atrial arrhythmia, myocardial infarction. In referral centres and selected patients, EPP is a cytoreductive or radical surgical treatment in extended pleural malignancies. Prospective studies are needed to standardise the timing of the procedure in a multimodality treatment program, according to the oncological and functional indications, to keep an acceptable complications rate and post-operative quality of life status.