Over the past few decades, anisotropic polymer particles are of significant interest because of their unique properties which can be applied in various areas, such as drug delivery, biotechnology, and electronics. Most approaches to synthesize anisotropic polymer particles, however, are complicated, and the three-dimensional shapes of the anisotropic particles are usually difficult to be controlled. In this work, we develop a solvent on-film annealing (SOFA) method to fabricate anisotropic polymer particles by studying the morphological evolution of polystyrene (PS) microspheres on poly(methyl methacrylate) (PMMA) films annealed in toluene vapor. At different annealing stages, the isotropic PS microspheres gradually transform to anisotropic PS particles with different morphologies, such as UFO-, cymbal-, peanut-, and bowl-shaped particles. The morphology evolution is driven by the surface and interfacial tensions during the annealing processes and can be confirmed by a selective removal technique. Acetic acid, a selective solvent for PMMA, and cyclohexane, a selective solvent for PS, are also used as the annealing solvents to further investigate the effect of the annealing solvent.