A population balance model for the aggregation of iron oxide nanoflowers (IONfs) is presented. The model is based on the fixed pivot technique and is validated successfully for four kinds of aggregation kernels. The extended Derjaguin, Landau, Verwey, and Overbeek (xDLVO) theory is also employed for assessing the collision efficiency of the particles, which is pertinent to the total energy of the interaction. Colloidal stability experiments were conducted on IONfs for two dispersant cases—aqueous phosphate buffered saline solution (PBS) and simulated body fluid (SBF). Dynamic light scattering (DLS) measurements after 24-h of incubation show a significant size increase in plain PBS, whereas the presence of proteins in SBF prevents aggregation by protein corona formation on the IONfs. Subsequent simulations tend to overpredict the aggregation rate, and this can be attributed to the flower-like shape of IONfs, thus allowing patchiness on the surface of the particles that promotes an uneven energy potential and aggregation hindering. In silico parametric study on the effects of the ionic strength shows a prominent dependency of the aggregation rate on the salinity of the dispersant underlying the effect of repulsion forces, which are almost absent in the PBS case, promoting aggregation. In addition, the parametric study on the van der Waals potential energy effect—within common Hamaker-constant values for iron oxides—shows that this is almost absent for high salinity dispersants, whereas low salinity gives a wide range of results, thus underlying the high sensitivity of the model on the potential energy parameters.