Introduction: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis appears an autoimmune disease characterized by neuropsychiatric symptoms, but the molecular mechanisms bridging brain structural alterations and gene expression remain unclear. This study aimed to explore the associations between Morphometric Inverse Divergence (MIND) abnormalities and transcriptional profiles in anti-NMDAR encephalitis, integrating multimodal analyses of neuroimaging, transcriptomics, neurotransmitter systems, and cell-type specificity, with a particular focus on identifying structural and molecular signatures underlying cognitive dysfunction. Methods: Thirty - seven healthy controls and 37 anti-NMDAR encephalitis patients were enrolled, and analyzed for MIND region values between groups. Using transcriptomic data from the Allen Human Brain Atlas, Partial Least Squares (PLS) regression was applied to analyze spatial correlations between regional MIND changes and gene expression. Functional enrichment, Protein-Protein Interaction (PPI) networks, neurotransmitter receptor/transporter analyses, and cell-type assignment were further performed to explore molecular pathways potentially linked to cognitive impairment. Results: Significant global and regional MIND abnormalities were presented in anti-NMDAR encephalitis patients, with increased values in regions such as the left paracentral cortex, insula, and cingulate cortex, involving multiple Yeo 7 functional networks (default mode and limbic networks). PLS regression identified genes associated with MIND changes, enriched in metabolic pathways, synaptic processes, and signaling pathways. Neurotransmitter systems (glutamate, gamma-aminobutyric acid) and cell types (astrocytes, excitatory/inhibitory neurons) were implicated in these associations, supporting a model of excitation-inhibition imbalance as a driver of both network disruption and cognitive impairment. Conclusion: This study reveals multidimensional mechanisms linking macroscale brain structural abnormalities, microscale gene expression, and neurotransmitter dysfunction in anti-NMDAR encephalitis, providing insights for developing imaging-based biomarkers of cognitive decline and molecularly targeted strategies for cognitive restoration in affected patients.