Technological advancements, changes in pharmacy students' learning preferences, and increased educational costs have necessitated the development and implementation of innovative teaching modalities. The University of Pittsburgh, School of Pharmacy has been using simulation-based learning throughout the curriculum for several years. To further advance this practice, a novel course was designed to teach students new concepts through online video lectures, slide sets and quizzes, and knowledge application during weekly practica time involving multiple patient cases taught with high fidelity simulation. While this course has been well received by students, it does require resources, organization, and time for development. In this article, we describe our experience developing, modifying, and sustaining this blended course with the hope that sharing our experiences over the past six years will lead to expediting successes at other institutions. Tips for success such as keeping online segments short, holding students accountable, thinking of simulation approaches beyond the mannequin, and developing standardized assessment tools are discussed. Overall the blended course of online learning and simulation is a unique educational experience akin to real-world pharmacy practice and is worth the effort with a goal of optimizing learning.