Scanning tunneling microscopy (STM) manipulation has received wide attention in the surface science community since the pioneering work of Eigler to construct surface nanostructures in an atom by atom fashion. Lots of scientists have been inspired and devoted to study the surface issues with the help of STM manipulations and great achievements have been obtained. In this Minireview, we mainly describe the recent progress in applying STM manipulations to regulate the inter-adsorbate and adsorbate–substrate interactions on solid surfaces. It was shown that this technique could not only differentiate intermolecular interactions but also construct molecular nanostructures by regulating different kinds of inter-adsorbate interactions or adsorbate–substrate interactions.