Background: Meningiomas are the most common primary central nervous system tumours in the adults, accounting for approximately 30% of intracranial tumours. NF2 alterations are the most common genetic abnormality in meningiomas and are known to initiate events for aggressive-type meningiomas. The purpose of this study was to explore genomic characteristics of co-mutated genes in NF2 meningiomas. Methods: This study retrospectively analyzed the genomic alteration of 347 Chinese Meningioma patients during 2019-2022. Next-generation sequencing (NGS) was performed to detect gene mutations in tumor samples of the patients. Results:NF2 mutations were observed in 160 of 347 patients (46%). Our results showed the NF2-mutant patients tended to have older age compared with NF2-wildtype patients (average age: 56 vs. 47, p < 0.05), and meningiomas were more common in women in both groups. TERT promoter mutation or CDKN2A/B deletion occurred in 16/160 (10%) of all NF2-mutant meningiomas. The proportion of NF2 alterations in tumors that harbored CDKN2A/B deletion or TERT promoter mutation was similar to those without mutations (41.0% vs. 46.8%, χ2＝0.46, p > 0.05). 11 patients defined as NF2-mutant meningiomas were found to co-occurred with POLR2A (n = 3), TRAF7 (n = 3), PIK3CA (n = 2), PIK3R1 (n = 2), AKT1 (n = 1), SMO (n = 1), which were previously reported in a mutually exclusive pattern, identifying unique clinical cohorts. Surprisingly, we observed co-mutation in [NF2 -TRAF7- PIK3CA] genes in a 43-year-old woman meningioma patient. Conclusions: In summary, NF2-mutant patients were observed in 46% Chinese meningioma population and tended to have older age. Interestingly, POLR2A, TRAF7, PIK3CA, PIK3R1, AKT1 and SMO mutations are reported as exclusive of NF2 mutations, were observed in 11 NF2-mutant patients in this study. The co-mutation of different driver genes in meningioma should be given enough attention, and their clinical significance remain further study.