Well-structured and monodisperse nanocomposite spheres with a magnetic core/mesoporous silica shell structure (MCMS) were obtained. The effects on the structure and morphology of the MCMS spheres were investigated under various synthesis conditions, including reaction time, quantity of silicate sources of tetraethoxysilane (TEOS) and n-octadecyltrimethoxysilane (C18TMS), ratio of TEOS/C18TMS, and ratio of H2O/EtOH in the starting solution. The particle size of the MCMS spheres and pore diameter are tunable in a certain range with 100% yield. A synthesis mechanism of the mesoporous silica shell was proposed that proceeds via three main stages. The silica shell proved to be effective on protecting the cores from leaching out in acidic conditions.