Where things go wrong in the brain matters. Gene dysregulation during brain development in key structures of the brain can result in neurodevelopmental disorders (NDD). Multiomics provides the bridge to resolving a large gap in the diagnosis, prognosis, and treatment of NDD because up until now, the uncertainty for clinical aspects of NDD lie in large part due their high clinical and genetic heterogeneity. Interpreting NDD risks genes is further complicated by understanding their regulation in relation to where they are expressed spatially during brain development. This talk focuses on using a multiomic approach to elucidating the relationship between NDD genes, their regulation in the context of the developing human cortex, an affected structure in NDD. Using both single nuclei (sn) and spatial RNAseq, a high resolution atlas of the developing human prefrontal cortex, neocortex, thalamus and striatum revealed refined subregional transcriptional identities. To understand these cell identities, a gene regulatory network (GRN) was constructed using genes associated with autism, bipolar disorder, major depressive disorder, schizophrenia and syndromic NDD against >1000 known transcription factors (TFs) to identify master transcriptional regulators of human brain development. Next, we harnessed snATACseq and our GRN for cell specific epigenomic profiling. Our multiomic approach idiscovered the repertoire of TFs that regulate NDD genes during brain development and resolved subcortical regions of the developing human brain which are not seen by snATACseq, ChIPseq, sn or spatialRNAseq alone.These multiomic approaches provide a framework to understanding how single cell epigenome/transcriptome and spatial data give us valuable insight into spatial representation of cell populations that influence disease pathogenesis.