Inside a cell, thousands of different genes function collectively to give rise to cellular behavior. Understanding the emergent behaviors of cells requires imaging at the genomic scale, which promises to transform our understanding in many areas of biology, such as regulation of gene expression, development of cell fate, and organization of distinct cell types in complex tissues. We developed a genomic-scale imaging method, MERFISH, which allows simultaneous imaging of hundreds to thousands of genes in individual cells and facilitates the delineation of gene regulatory networks, the mapping of molecular distribution inside cells, and the mapping of distinct cell types in complex tissues. We have also extended this approach to image numerous genomic loci and trace the 3D structure of chromosomes in single cells. I will describe the technology development of MERFISH and its applications, focusing on generating the cell atlas of complex tissues and mapping the 3D organization of the genome.