The Plateau-Rayleigh instability is a phenomenon driven by the reduction of the surface energies, in which a liquid cylinder transforms to a series of droplets with distinct spacing. This instability phenomenon is also applied broadly for the transformation of cylindrical materials to spherical particles in homogeneous environments. The demonstration of the instability in heterogeneous environments, however, has been less studied. Here, we study the Plateau-Rayleigh instability of electrospun polystyrene (PS)/poly(methyl methacrylate) (PMMA) core-shell fibers annealed on n-octadecyl-trichlorosilane (ODTS)-modified glass substrates with toluene vapors. After the annealing procedures, the PS/PMMA core-shell fibers transform to anisotropic sunny-side-up egg-shaped polymer structures, driven by the reduction of the total surface and interfacial energies. Quantitative analyses are performed on the sizes of the structures. Fluorescent fibers are also prepared by electrospinning and annealed on the ODTS-modified substrates, demonstrating the potential application as fluorescence manipulation platforms.