One essential tool in pharmaceutical analysis is the Ratio Difference Method (RDM), which provides a sophisticated method for breaking down the complexity of drug mixes. This paper explores the nuances of the RDM and how it might be applied to improve drug combination analysis's accuracy and effectiveness. Through a careful comparison of the ratios of the individual medications in a combination, the RDM helps researchers identify tiny differences and distinguish between different components with more precision. The theoretical foundations of the RDM are explained in this overview, along with its guiding principles and methods. It also examines a wide range of real-world situations, from pharmacokinetic research to quality control evaluations, in which the RDM has proven useful. Through a synthesis of recent advancements and case studies, this article underscores the versatility and utility of the RDM in addressing the evolving challenges of pharmaceutical analysis. Emphasizing its role in enhancing drug formulation strategies, optimizing therapeutic regimens, and elucidating complex drug interactions, this review advocates for the widespread adoption of the RDM as a cornerstone technique in contemporary pharmaceutical research and development.