Parenteral depot formulations have garnered significant attention due to their ability to provide controlled release of drugs. Despite advancements in depot formulation technology, the market availability of parenteral microsphere products remains limited. This scarcity can be attributed to challenges such as low yield, inconsistent batch-to-batch reproducibility, high costs of polymers, and the complexity of manufacturing processes. This study aims to systematically identify and optimize the critical material attributes and process parameters associated with the coacervation method used in PLGA based microsphere manufacturing. The results of this investigation provide conclusive insights into several key factors, including the selection of polymers based on desired release profiles (influenced by inherent viscosity), the impact of drug concentration on formulation, the effects of different types and rates of coacervating agent addition during microsphere production, and the optimization of organic solvent ratios. By assessing the influence of various parameters on critical quality attributes, this study contributes to enhancing the understanding and optimization of microsphere manufacturing via the coacervation method in parenteral depot formulations.