We have studied the structural, electrical, and optical properties of La0.05Sr0.95SnO3 thin films, which exhibited a strong dependence upon the substrate’s orientation and strain. X-ray diffraction results show that the LSSO films grow epitaxially on (001) and (011)-oriented LaAlO3 substrates, and the in-plane compressive strain decreases gradually upon increasing film thickness. Room-temperature resistivity varies from 4.23 (13.0) to 1.37 (4.76) mΩ cm as the film thickness increases for (001) orientation ((011) orientation). Temperature dependent resistivity curves of all the samples show a metal–semiconductor transition (MST), which can be explained by the electron–electron interactions below MST rather than weak localization. Both reducing the in-plane compressive strain and transferring the orientation from (011) to (001) can drive the MST point shifts toward lower temperature, indicative of the enhancement of the metallic transport in the films. The band gap increases upon increasing film thickness due to Burstein-Moss effect. The charge distributions of Sn and O from density functional theory (DFT) calculations illustrate that (001)-plane has a better conductivity. Furthermore, our DFT results also demonstrate that decreasing the in-plane strain will lead to a smaller electron effective mass, thus the increased carrier mobility can be obtained. These comprehensive investigations advance our knowledge of the optoelectronic characteristics and provide valuable insights for future research in related transparent materials.