Cells respond to both mechanical and topographical stimuli by reorienting and reorganizing their cytoskeleton. Under certain conditions, such as for cells on cyclically stretched grooved substrates, the effects of these stimuli can be antagonistic. The biophysical processes that lead to the cellular reorientation resulting from such a competition are not clear yet. In this study, we hypothesized that mechanical cues and the diffusion of the intracellular signal produced by focal adhesions are determinants of the final cellular alignment. This hypothesis was investigated by means of a computational model, with the aim to simulate the (re)orientation of cells cultured on cyclically stretched grooved substrates. The computational results qualitatively agree with previous experimental studies, thereby supporting our hypothesis. Furthermore, cellular behavior resulting from experimental conditions different from the ones reported in the literature was simulated, which can contribute to the development of new experimental designs.