Understanding why men and women show different susceptibilities to neurological and psychiatric conditions has long puzzled researchers. This breakthrough analysis reveals that sexual dimorphism in the brain extends far deeper than previously recognized, with profound implications for personalized medicine and our understanding of brain disorders. Examining brain tissue from 30 adults across six cortical regions, scientists identified over 3000 genes that exhibit sex-biased expression patterns. The fusiform cortex showed the most pronounced differences, while glial cells and excitatory neurons displayed the strongest sex-specific signatures. Among these, 133 genes demonstrated consistent sex-based expression differences across all brain regions and cell types examined. The research employed single-cell RNA sequencing technology to achieve unprecedented resolution, analyzing individual cell populations rather than bulk tissue. This granular approach revealed that sex chromosome genes contributed significantly to the observed differences, but autosomal genes also played crucial roles. The identified gene signatures connect directly to cortical architecture development, hormone-responsive pathways, and genetic susceptibility factors for sex-biased neurological disorders. These findings represent a paradigm shift from viewing male-female brain differences as primarily structural to recognizing extensive molecular-level variation. The implications extend beyond basic neuroscience to clinical applications, suggesting that therapeutic approaches for conditions like autism, depression, and Alzheimer's disease may need sex-specific considerations. However, the study's limitation to cortical regions means subcortical and brainstem differences remain unexplored. This comprehensive molecular atlas provides the foundation for developing precision medicine approaches that account for biological sex in treating brain disorders.