Scanning tunneling microscope (STM) has presented a revolutionary methodology to nanoscience and nanotechnology. It enables imaging of the topography of surfaces, mapping the distribution of electronic density of states, and manipulating individual atoms and molecules, all at atomic resolutions. In particular, atom manipulation capability has evolved from fabricating individual nanostructures toward the scalable production of the atomic‐sized devices bottom‐up. The combination of precision synthesis and in situ characterization has enabled direct visualization of many quantum phenomena and fast proof‐of‐principle testing of quantum device functions with immediate feedback to guide improved synthesis. Several representative examples are reviewed to demonstrate the recent development of atomic‐scale manipulation, focusing on progress that addresses quantum properties by design in several technologically relevant materials systems. Integration of several atomically precisely controlled probes in a multiprobe STM system vastly extends the capability of in situ characterization to a new dimension where the charge and spin transport behaviors can be examined from mesoscopic to atomic length scale. The automation of atomic‐scale manipulation and the integration with well‐established lithographic processes further push this bottom‐up approach to a new level that combines reproducible fabrication, extraordinary programmability, and the ability to produce large‐scale arrays of quantum structures. The recent developments in atomic‐scale manipulation with scanning tunneling microscopy (STM) are reviewed. In particular, the review focuses on the progress that addresses quantum properties by design through the precise control of atomic structures in several technologically relevant materials systems. In situ characterization with single‐ and multiprobe STM is discussed, which is utilized for thorough determination of electronic structures.