Malignant pleural mesothelioma (MPM) is a devastating disease caused by asbestos exposure. The pathophysiology and genomic landscape of MPM have been well-researched, but more must be understood to improve disease outcomes. The metabolome of MPM is mostly unexplored and could contain biologically relevant information. The goal of this thesis is to uncover mechanisms of MPM via the metabolomic profiling of patient-derived MPM cell lines and their parent tumours. First, a gas chromatography–mass spectrometry (GC-MS) protocol for rapid, semi-targeted profiling of cellular metabolites from commercially available MPM cell lines was optimised. Second, a wider, untargeted ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) platform was applied to characterise compounds from primary MPM cell lines, with regards to pathophysiology. Then, cellular metabolites identified were mapped to typical gene copy number variations (CNVs) to identify key interactions. To conclude, the reported metabolomes of primary MPM cell lines and parent tumours were analysed to identify robust mechanisms observable in both cell lines and tumours. Metabolomic analysis of MPM revealed associations between sphingolipid metabolism and biphasic pathology. Additionally, an association between 9p21.3 locus deletion and tryptophan metabolism was observed. Similarly, loss of the neurofibromin-2 (NF2) gene in primary cell lines and tumours resulted in increased long-chain acylcarnitine abundance. These findings, along with the novel analysis pipeline described in this thesis, contribute to the growing body of research aiming to understand and combat MPM.