Freeze-drying, until now, has been a process that was designed using a trial and error experimental approach. This approach is often material and time consuming, and the resulting freeze-drying processes are neither optimum nor robust. Accordingly, the objective of this study was to develop a simple-to-use and experimental-based approach to design an optimum and robust freeze-drying process for any given formulation. The temperature ramp approach (TRA) detailed in this study involves the implementation of a customized design of experiments (DoE) to perform few (three or four) experiments using a given drug formulation. The DoE results are analyzed to define optimum processing conditions (i.e., shelf temperature and chamber pressure) based on a predefined range of target product temperature for primary drying, which could be defined from formulation characterization at its frozen state. In this study, a successful freeze-drying process of two model formulations using the TRA was designed. Verification experiments at the optimum processing conditions showed excellent agreement in both product temperature and sublimation rate with the values obtained using the TRA. Thus, the TRA detailed in this study offers a significant advantage to reduce development time and material, and enhance the efficiency and robustness of the resulting freeze-drying process.