Drug delivery is an integral part of the drug development process, influencing safety and efficacy of active pharmaceutical ingredients. The application of nanotechnology has enabled the discovery of novel formulations for numerous therapeutic purposes across multiple disease areas. However, evaluation of novel formulations in clinical scenarios is slow and hampered due to various ethical and logistical barriers. Computational models have the ability to integrate existing domain knowledge and mathematical correlations, to rationalize the feasibility of using novel formulations for safely enhancing drug delivery, identifying suitable candidates, and reducing the burden on preclinical and clinical studies. In this review, types of novel formulations and their application through several routes of administration and the use of modeling approaches that can find application in different stages of the novel formulation development process are discussed.