Adsorption of two typical pharmaceuticals and personal care products (PPCPs) (meloxicam and naproxen) onto core shell Fe3O4@MIL-100(Fe) on the basis of optimal parameters such as the effect of pH, the amount of adsorbent, coexisting ions, and the varying concentration has been described. Adsorption kinetic data were modeled using the pseudo-first-order and the pseudo-second-order kinetic equations. Kinetic studies showed better applicability for the pseudo-first-order model, indicating the process controlled by the chemical reaction. The Freundlich isotherm model was more suitable to describe the adsorption equilibrium data than the Langmuir model, suggesting that the adsorption process was multilayer adsorption. The thermodynamic paraments obtained indicate that the adsorption on Fe3O4@MIL-100(Fe) was a spontaneous, endothermic, and entropy-increasing process. In addition, the molecular simulation was used to elucidate the molecular interactions and free binding energies between Fe3O4@MIL-100(Fe) and two targets and explained the adsorption mechanism of the host and the guest. The segregative and renewable properties of core-shell Fe3O4@MIL-100(Fe) make it widely used in the removal of PPCPs from an aqueous solution, which will be beneficial for commercial exploitations.