The synthesis of NPs can be a complicated and demanding process to understand. Through using DoE, the intricate reaction process can be studied and modelled, allowing for the re-action outcome to be predicted in relation to the experimental domain used. In this study, the synthesis of SPION@SiO 2 NPs through a microemulsion method has been modelled using a 3 3 full-factorial design. Following regression analysis, the silica shell thickness was found to be linearly dependent on the number of moles of TEOS, and the interaction between the number of moles of NH 4 OH and fractionated additions of TEOS, whereby increasing these terms were observed to increase the size of particles formed. Similarly the nanoparticle dispersity was dependent on the linear effect of the number of moles of TEOS, and the interaction between the number of moles of NH 4 OH and fractionated additions of TEOS. In this case, the increase in one of these terms resulted in the reduction in nanoparticle dispersity. The population of SPION@SiO 2 NPs was effected by the interaction between TEOS and NH 4 OH, and not impacted by the fractionated addition of TEOS. The complexity of the model was reflective of the synthesis mechanism, where each of the reagents hold multiple roles that are dependent on each other in controlling the properties of the produced NPs. Through using a DoE approach, these underlying trends were identified and modelled and could be used for the optimisation of or tailoring of SPION@SiO 2 NPs with controlled properties.