This research focuses on the architectural design of the silica shell on the Fe3O4 nanoparticle to precisely control and minimize its thickness, with the aim of achieving a final product with optimal saturation magnetization (Ms) for biomedical applications. A rapid and facile microwave-assisted synthesis method was developed for the synthesis of Fe3O4@SiO2 and Fe3O4@SiO2@NH2 core–shell nanoparticles with ultra-thin SiO2 shells and excellent magnetic performance. The particle size distribution of the Fe3O4@SiO2 nanoparticles was in the range of 15–35 nm, with a mean particle size of approximately 21 nm. The mean thickness of the SiO2 shells on the Fe3O4 cores was found to be 3 nm. FTIR analysis also confirmed the successful silica coating on Fe3O4 nanoparticles and the successful amino-functionalization of silica-coated Fe3O4 nanoparticles. The Ms of Fe3O4, Fe3O4@SiO2, and Fe3O4@SiO2@NH2 nanoparticles were found to be 64.4, 59.8, and 52.4 emu/g, respectively. It has been confirmed that the ultra-thin SiO2 coating has a negligible effect on the magnetic characteristics of the nanoparticles. The developed microwave-assisted synthesis method in this study not only provides an interesting, rapid, and facile synthesis route but also results in a product with a narrow particle size distribution, an ultra-thin SiO2 shell, favorable magnetic properties, and improved cell compatibility, which may be used in several different applications, particularly biomedical applications.