Recent developments in the field of mechanobiology have renewed the call for a better understanding of the role of mechanical forces as potent regulators and indicators of stem cell fate. Although it is well established that mechanical forces play a crucial role in guiding tissue development, little is known about how submicroscopic biomechanical forces can influence key stem cell behaviors. This review will detail the use of micro-/nano-technologies that are advancing our current understanding of stem cell mechanobiology, and mechanoregulation of stem cell fate using engineered surface topographies and small-scale patterning techniques. The involvement of focal adhesions and the cytoskeleton systems as a common biophysical impetus through which these mechanical signals are transduced via distinct signaling pathways will also be discussed. These insights are envisioned to provide the basis for the rational design of future biocompatible materials and may inspire alternative drug-free therapeutic strategies to manage diseased sites via biomechanical management.