The COVID-19 pandemic, which began in Wuhan, China, at the end of 2019, has catalyzed global efforts in drug development. Modeling approaches are essential for understanding the virus and developing effective therapies. This review highlights the role of in vitro, in vivo, and in silico models in expediting drug discovery and optimization. In vitro models, such as cell cultures and organoids, offer insights into viral biology and drug effects. In vivo models, including animal studies and clinical trials, assess drug efficacy and safety. In silico approaches, like molecular dynamics simulations and molecular docking, accelerate drug discovery by predicting compound-target interactions. Drug repurposing, exemplified by remdesivir, has shown promise in treating COVID-19. Integrating these modeling techniques facilitates the rapid identification of effective treatments and optimization of dosing regimens. Insights from disease modeling underscore the importance of both regional and global strategies. Continued advancement in these models is vital for expanding therapeutic options against COVID-19.