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Objective To investigate whether methionine metabolic axis could be a potential therapeutic target for multiple myeloma (MM). Methods Ten MM patients (newly diagnosed and treatment-responsive groups) were selected from the Department of Hematology, and five healthy individuals who voluntarily donated bone marrow supernatant from the Affiliated Hospital of Guangdong Medical University were chosen as the control group. Targeted quantitative metabolomics analysis of bone marrow supernatants from the three groups was performed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Multivariate statistical analysis was conducted on the metabolomics data. Human MM-related high-throughput gene chip data from the NCBI GEO database were analyzed using online tools Cell Ranger and Seurat software, and bioinformatics analysis techniques were used to identify common differential genes. Key genes related to the methionine metabolism axis in MM were screened. Results The levels of methionine and cysteine in the bone marrow supernatants of MM patients were significantly elevated (P<0.05). Enzymes involved in the methionine cycle, including methionine adenosyltransferase 2 A (MAT2 A), adenosylhomocysteinase (AHCY), and protein arginine methyltransferase 1 (PRMT1), were found to be associated with MM progression. Conclusion The key enzymes MAT2 A, AHCY, and PRMT1 may influence the biological behavior and disease progression of MM by regulating methionine metabolism. [ABSTRACT FROM AUTHOR]