This article reviews the current status, development, opportunities, challenges, and prospects in the diagnosis and treatment of brain tumor-related epilepsy (BTRE) based on multi-omics technologies. BTRE is a leading cause of intractable epilepsy, with a complex etiology involving genetic and molecular biomarkers. Advances in genomics, transcriptomics, epigenomics, proteomics, and metabolomics have provided valuable insights into the pathophysiological mechanisms and biomarkers of BTRE. Key findings include the role of the BRAF gene in BTRE development, the association between IDH variants and glioma-related epilepsy, and the involvement of miRNAs and lncRNAs in BTRE progression. Proteomics studies have identified dynamic changes in protein acetylation and the expression of specific proteins such as AQP-4 and BCL2A1. Metabolomics research has highlighted the importance of the PI3K/AKT/mTOR pathway and the potential of SV2A, P-gb, and CAD65/67 as biomarkers for BTRE. The review also discusses the associated mechanisms of BTRE, including the role of glutamate and GABA neurotransmitters, and the impact of ion transporters like KCC2 and NKCC1. Despite the progress, there is a need for more comprehensive omics studies on peripheral tumor tissues and larger sample sizes to further understand the correlation between peritumoral tissues and seizures in glioma patients. The integration of omics technologies with data retrieval systems and databases will be crucial for advancing the field of BTRE research.This article reviews the current status, development, opportunities, challenges, and prospects in the diagnosis and treatment of brain tumor-related epilepsy (BTRE) based on multi-omics technologies. BTRE is a leading cause of intractable epilepsy, with a complex etiology involving genetic and molecular biomarkers. Advances in genomics, transcriptomics, epigenomics, proteomics, and metabolomics have provided valuable insights into the pathophysiological mechanisms and biomarkers of BTRE. Key findings include the role of the BRAF gene in BTRE development, the association between IDH variants and glioma-related epilepsy, and the involvement of miRNAs and lncRNAs in BTRE progression. Proteomics studies have identified dynamic changes in protein acetylation and the expression of specific proteins such as AQP-4 and BCL2A1. Metabolomics research has highlighted the importance of the PI3K/AKT/mTOR pathway and the potential of SV2A, P-gb, and CAD65/67 as biomarkers for BTRE. The review also discusses the associated mechanisms of BTRE, including the role of glutamate and GABA neurotransmitters, and the impact of ion transporters like KCC2 and NKCC1. Despite the progress, there is a need for more comprehensive omics studies on peripheral tumor tissues and larger sample sizes to further understand the correlation between peritumoral tissues and seizures in glioma patients. The integration of omics technologies with data retrieval systems and databases will be crucial for advancing the field of BTRE research.