Solid tumours comprise many different cell types organized in spatially structured arrangements, with substantial intratumour and intertumour heterogeneity. Advances in spatial profiling technologies over the past decade hold promise to capture the complexity of these cellular architectures to build a holistic view of the intricate molecular mechanisms that shape the tumour ecosystem. Some of these mechanisms act at the cellular scale and are controlled by cell-autonomous programmes or communication between nearby cells, whereas other mechanisms result from coordinated efforts between large networks of cells and extracellular molecules organized into tissues and organs. In this Review we provide insights into the application of single-cell and spatial profiling tools, with a focus on spatially resolved transcriptomic tools developed to understand the cellular architecture of the tumour microenvironment and identify opportunities to use them to improve clinical management of cancers.