BackgroundDetermining the grade and molecular marker status of intramedullary gliomas is important for assessing treatment outcomes and prognosis. Invasive biopsy for pathology usually carries a high risk of tissue damage, especially to the spinal cord, and there are currently no non-invasive strategies to identify the pathological type of intramedullary gliomas. Therefore, this study aimed to develop a non-invasive machine learning model to assist doctors in identifying the intramedullary glioma grade and mutation status of molecular markers.MethodsA total of 461 patients from two institutions were included, and their sagittal (SAG) and transverse (TRA) T2-weighted magnetic resonance imaging scans and clinical data were acquired preoperatively. We employed a transformer-based deep learning model to automatically segment lesions in the SAG and TRA phases and extract their radiomics features. Different feature representations were fed into the proposed neural networks and compared with those of other mainstream models.ResultsThe dice similarity coefficients of the Swin transformer in the SAG and TRA phases were 0.8697 and 0.8738, respectively. The results demonstrated that the best performance was obtained in our proposed neural networks based on multimodal fusion (SAG-TRA-clinical) features. In the external validation cohort, the areas under the receiver operating characteristic curve for graded (WHO I–II or WHO III–IV), alpha thalassemia/mental retardation syndrome X-linked (ATRX) status, and tumor protein p53 (P53) status prediction tasks were 0.8431, 0.7622, and 0.7954, respectively.ConclusionsThis study reports a novel machine learning strategy that, for the first time, is based on multimodal features to predict theATRXandP53mutation status and grades of intramedullary gliomas. The generalized application of these models could non-invasively provide more tumor-specific pathological information for determining the treatment and prognosis of intramedullary gliomas.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12916-023-02898-4