Perfluorocarbon (PFC) filled nanoparticles are increasingly being investigated for various biomedical applications. Common approaches for PFC liquid entrapment involve surfactant-based emulsification and Pickering emulsions. Alternatively, PFC liquids are capable of being entrapped inside hollow nanoparticles via a postsynthetic loading method (PSLM). While the methodology for the PSLM is straightforward, the effect each loading parameter has on the PFC entrapment has yet to be investigated. Previous work revealed incomplete filling of the hollow nanoparticles. Changing the loading parameters was expected to influence the ability of the PFC to fill the core of the nanoparticles. Hence, it would be possible to model the loading mechanism and determine the influence each factor has on PFC entrapment by tracking the change in loading yield and efficiency of PFC-filled nanoparticles. Herein, neat PFC liquid was loaded into silica nanoparticles and extracted into aqueous phases while varying the sonication time, concentration of nanoparticles, volume ratio between aqueous and fluorous phases, and pH of the extraction water. Loading yields and efficiency were determined via 19F nuclear magnetic resonance and N2 physisorption isotherms. Sonication time was indicated to have the strongest correlation to loading yield and efficiency; however, method validation revealed that the current model does not fully explain the loading capabilities of the PSLM. Confounding variables and more finely controlled parameters need to be considered to better predict the behavior and loading capacity by the PSLM and warrants further study.