Background <p>Trabectedin, a marine-derived antineoplastic agent, has shown promise in various malignancies, prompting investigation into its efficacy for high-grade meningiomas.</p> Objective <p>This systematic review aims to evaluate the efficacy and safety of trabectedin in the management of high-grade meningiomas by synthesizing data from existing randomized controlled trials (RCTs).</p> Methods <p>Comprehensive searches were conducted in PubMed, the Cochrane Database of Systematic Reviews (CDSR), and Epistemonikos using MeSH terms for “Trabectedin” and “Meningioma.” Studies were included if they focused on trabectedin treatment in meningioma patients and were RCTs. Preclinical studies and trial protocols were excluded. Data extraction included study design, patient characteristics, intervention details, outcomes, and adverse events. Quality assessment was conducted using the Cochrane Risk of Bias tool.</p> Results <p>we got three RCTs, with one meeting the inclusion criteria. This RCT, conducted by Preusser et al., involved 90 patients with recurrent WHO grade 2 or 3 meningiomas. The trabectedin arm showed an overall survival of 13.54 months compared to 10.61 months in the local standard of care (LSOC) arm. However, progression-free survival (PFS) was shorter in the trabectedin arm (2.43 months) compared to the LSOC arm (4.17 months). The quality assessment revealed a high risk of bias due to the open-label design.</p> Conclusion <p>Trabectedin demonstrates a modest survival benefit in patients with high-grade meningiomas. The high risk of bias and limited sample size underscore the need for larger, double-blind RCTs to validate these findings. Further research should explore combination therapies and identify biomarkers to optimize treatment efficacy and patient selection.</p>