Multiphysics modeling is an emerging approach in cellular bioengineering research, used for simulating complex biophysical interactions and their effects on cell viability and function. Our goal in the present study was to integrate cell-specific finite element modeling—which we have developed in previous research to simulate deformation of individual cells subjected to external loading—with oxygen transport in the deformed cells at normoxic and hypoxic environments. We specifically studied individual and combined effects of substrate stretch levels, O2 concentration in the culture media, and temperature of the culture media on intracellular O2 levels in cultured myoblasts, in models of two individual cells. We found that (i) O2 transport became faster with the increasing levels of substrate stretch (ranging from 0 to 24%), and (ii) the effect of a 3 °C temperature drop on slowing down the O2 transport was milder with respect to the effect that strains had. The changes in cell geometry due to externally applied deformations could, hence, theoretically affect cell respiration, which should be a consideration in cellular mechanics experiments.