2D materials and heterostructures have attracted significant attention for a variety of nanoelectronic and optoelectronic applications. At the atomically thin limit, the material characteristics and functionalities are dominated by surface chemistry and interface coupling. Therefore, methods for comprehensively characterizing and precisely controlling surfaces and interfaces are required to realize the full technological potential of 2D materials. Here, the surface and interface properties that govern the performance of 2D materials are introduced. Then the experimental approaches that resolve surface and interface phenomena down to the atomic scale, as well as strategies that allow tuning and optimization of interfacial interactions in van der Waals heterostructures, are systematically reviewed. Finally, a future outlook that delineates the remaining challenges and opportunities for 2D material interface characterization and control is presented. Realistic applications of 2D materials require nanoscale characterization and control over surfaces and interfaces. After introducing related surface and interface phenomena, characterization techniques and control strategies that have been applied to the surfaces and interfaces of 2D materials and heterostructures are comprehensively reviewed. In addition, the remaining challenges and opportunities in this emerging field are delineated.