Glioma, a malignant intracranial tumor with high invasiveness and heterogeneity, significantly impacts patient survival. This study integrates multi-omics data to improve prognostic prediction and identify therapeutic targets. Using single-cell data from glioblastoma (GBM) and low-grade glioma (LGG) samples, we identified 55 distinct cell states via the EcoTyper framework, validated for stability and prognostic impact in an independent cohort. We constructed multi-omics datasets of 620 samples, integrating transcriptomic, copy number variation (CNV), somatic mutation (MUT), Microbe (MIC), EcoTyper result data. A scRNA-seq enhanced Self-Normalizing Network-based glioma prognosis model achieved a C-index of 0.822 (training) and 0.817 (test), with AUC values of 0.867, 0.876, and 0.844 at 1, 3, and 5 years in the training set, and 0.820, 0.947, and 0.936 in the test set. Gradient attribution analysis enhanced the interpretability of the model and identified key molecular markers. The classification into high- and low-risk groups was validated as an independent prognostic factor. HDAC inhibitors are proposed as potential treatments. This study demonstrates the potential of integrating scRNA-seq and multi-omics data for robust glioma prognosis and clinical decision-making support.