A framework is proposed to explain the dissolution and fragmentation of particles during friction stir welding and processing. Two major mechanisms dissolve the particle during the process: (i) thermally activated diffusion, and (ii) dislocation and grain boundary sweeping of atoms. We use a three-dimensional coupled viscoplastic flow and heat transfer model to quantify these mechanisms. For illustration purposes, calculations were done on a thermally stable Mg2Y intermetallic that dissolved during processing. The framework is universal and applies to any second phase dissolution and fragmentation during friction stir welding and processing, thus enabling a science-based approach to tailor microstructures.