The realization of the enormous potential of stem cells requires development of efficient bioprocesses and optimization drawing drawn from mechanobiological considerations. Here, we emphasize the importance of mechanotransduction as one of the governing principles of stem cell bioprocesses, underscoring the need to further explore the behavioral mechanisms involved in sensing mechanical cues and coordinating transcriptional responses. We identify the sources of the intrinsic, extrinsic, and external noise in bioprocess under uncertainty, and discuss criteria and indicators that might assess and predict cell-to-cell variability resulting from environmental fluctuations. Specifically, we propose a conceptual framework to explain the impact of mechanical forces within cellular environment and identify key cell state determinants in bioprocess and discuss their implementation challenges.