Malignant pleural mesothelioma (MPM) is an aggressive disease with limited treatment response and devastating prognosis. Exposure to asbestos and chronic inflammation are acknowledged as main risk factors. Since immune therapy evolved as a promising novel treatment modality, we want to reevaluate and summarize the role of the inflammatory system in MPM. This review focuses on local tumor associated inflammation on the one hand and systemic inflammatory markers, and their impact on MPM outcome, on the other hand. Identification of new biomarkers helps to select optimal patient tailored therapy, avoid ineffective treatment with its related side effects and consequently improves patient's outcome in this rare disease. Additionally, a better understanding of the tumor promoting and tumor suppressing inflammatory processes, influencing MPM pathogenesis and progression, might also reveal possible new targets for MPM treatment. After reviewing the currently available literature and according to our own research, it is concluded that the suppression of the specific immune system and the activation of its innate counterpart are crucial drivers of MPM aggressiveness translating to poor patient outcome.