Cell adhesion to the extracellular matrix is accomplished by the clustering of receptor–ligand bonds into focal contacts on the cell-substrate interface. The contractile forces applied onto these focal contacts lead to elastic deformation of the surrounding, which results into a cellular mechanosensory capability that plays a key role in cell adhesion, spreading, and migration, among many others. The mechanosensitivity can be manipulated by the substrate anisotropy, by which focal contacts may align into certain directions so to minimize the total mechanical potential energy. Using the elastic anisotropic contact analysis, this work systematically analyzes the dependence of the alignment on the elastic anisotropy, and more importantly, the direction of the inclined contractile forces. The contact displacement fields are a complex function of the elastic constants, so simple analysis based on tensile or shear softest direction cannot properly predict the alignment orientation. It is also proved that if these focal contacts are of elongated shape, the major axis will be parallel to the alignment direction.