To fully understand the regulation of gene expression in individual cells of a composite tissue requires the integration of different layers of molecular information, including epigenomic and transcriptomic data, in a spatially resolved manner and ideally at single-cell resolution. Whereas single-cell multi-omics approaches capture information from different molecular layers, spatial omics approaches have so far mainly been restricted to one layer at a time. Zhang et al. now describe two technologies for the spatially resolved co-mapping of epigenome and transcriptome at near single-cell resolution. They apply these technologies to mouse and human brain tissue to show their potential for informing our understanding of gene regulation within complex tissues.