Poor aqueous solubility is a major challenge in the formulation development of Biopharmaceutics Classification System (BCS) Class II drugs, which exhibit high permeability but low solubility. Various solubility enhancement techniques have been explored to improve the bioavailability of these drugs. The mixed solvency approach, an emerging and promising technique, involves the synergistic use of multiple solubilizers to enhance drug dissolution without relying on conventional organic solvents or surfactants. This review critically analyzes recent advancements in the mixed solvency approach, with a particular focus on the role of urea and xylenesulfonate as effective solubilizing agents. Their mechanism of action, impact on drug stability, and potential for large-scale application are discussed. Additionally, comparative evaluations with other solubility enhancement techniques, including solid dispersions, co-crystallization, and nano-formulations, are presented. The mixed solvency concept offers advantages such as reduced toxicity, environmental sustainability, and cost-effectiveness. However, challenges such as selection criteria for solubilizers, optimization of solubility parameters, and regulatory concerns need to be addressed for broader industrial adoption. This review provides valuable insights into the potential of mixed solvency as a sustainable solubility enhancement strategy for BCS Class II drugs, paving the way for improved drug formulation and therapeutic efficacy.