Optical spin-orbit interactions (SOI), demonstrated experimentally in optical cavities, enable the polarization degrees of freedom of light to be described and controlled as an effective pseudospin, providing a foundation for spintronic-like control of light and the development of next-generation optical technologies. However, prior works describe this emergent effect using phenomenological models that fail to uncover its microscopic quantum origins, and as a result, a rigorous connection between material electronic structure and the optical SOI remains elusive. In this work, we address this fundamental challenge by developing a microscopic quantum theory starting from the non-relativistic quantum electrodynamical (QED) description of light-matter interactions. We show that this effect arises from virtual interactions between confined photons and material excitations. Crucially, our theoretical framework provides microscopic material-design principles for tuning the distinct components of optical SOI, which include the optical birefringence, photonic self-energies, TE-TM splitting, and optical Zeeman splitting, enabling precise engineering of effective magnetic fields, diabolical points, and pseudospin textures. We anticipate that the predictive capability of our microscopic theory will enable systematic screening and design of material systems for photonic spintronics and optical technologies.