Interest in model-informed approaches across pharma and medicine have dramatically increased in recent years. For the first project in therapeutics, a modeling approach was utilized here to optimize rifampin dosing for orthopedic implant-associated S. aureus infection. With a mortality rate of 10-30%, current rifampin dosing regimens may provide inadequate exposures to infected bone tissue. An integrated approach using in vitro, in vivo, and human data, along with pharmacokinetic (PK) modeling and simulation, was utilized to suggest high-dose rifampin regimens are needed to optimize bone exposures, as bone penetration was shown to be much lower (10-15%) than previously thought. For the second project in generic drug development, a model-integrated bioequivalence (MIBE) framework was proposed to demonstrate the application of MIBE for generic companies. With our MIBE approach, we demonstrate how to prepare for, plan, and implement MIBE in a robust manner that lends credibility to the virtual assessment of bioequivalence from an abbreviated trial. With an example drug of Depo-SubQ Provera 104, we show that with MIBE we can reduce the trial size by 33-50%. Thus, we demonstrate in our work the ability to tackle complex challenges with model-informed approaches to optimize dose and to accelerate generic drug development.