The new temporal and spatial regimes of exploration enabled by nanoscience and nanotechnology have led to significant insights into fundamental processes that govern dynamics at the small scale of matter including bio-matter at the molecular scale. These abilities were enabled by breakthroughs in instrumentation that had to overcome fundamental sources of uncertainty such as thermal noise. In this talk, the primary challenges to nanoscale interrogation and manipulation will be presented in a systems perspective. Here, solution methodologies enabled by a modern control approach will be highlighted. With the exploration of biological processes at the molecular and cellular scale using nano-interrogation tools, it has become evident that evolution has endowed biology with remarkable machinery to perform and achieve precise functionality at the small scale in the presence of a highly uncertain environment. Understanding these bio-molecular systems, apart from providing key insights into biology and the related therapeutic impact, holds the promise for strategies to engineer material and systems at the small scale. Recent efforts into probing and understanding transport at the molecular scale and key proteins that provide structural integrity will be detailed to showcase the power of a control systems perspectives.