The holy grail in nanoelectronics is the construction of nanodevices with high density, low cost, and high performance per device and per integrated circuit. One approach is the fabrication of surface nanostructures and atomic-scale templates via the autonomous assembly of atoms and/or molecules on well-defined surfaces. To steer the atomic or molecular growth processes and create a wide range of surface nanostructures with desired properties, a comprehensive understanding of the mechanisms that control the surface self-assembly processes is required. The capability to manipulate the nanodevices at the submolecular level with good controllability is also of paramount importance. This review highlights some key recent developments in the fabrication of low-dimensional nanostructures based on supramolecular self-assembly on predefined surfaces, with particular emphasis on the rapidly expanding field of two-dimensional materials. Special attention is also given to the latest progress in single-molecule manipulation for future device applications.