The solubility of an active pharmaceutical ingredient (API) plays a pivotal role in determining its bioavailability after oral administration. Poor aqueous solubility, common among many new drug candidates, can lead to inconsistent absorption, necessitating higher doses and complex formulations, which in turn increase development costs. The Biopharmaceutical Classification System (BCS) highlights this challenge, especially for Class II and Class IV drugs, which exhibit low solubility. To address these issues, recent advancements have focused on enhancing solubility through innovative formulation techniques. Amorphous Solid Dispersions (ASDs), produced via Hot-Melt Extrusion (HME) and Spray Drying, improve dissolution by maintaining drugs in a high-energy amorphous state. Nanosuspensions increase surface area and dissolution rate by reducing particle size. Lipid-Based Drug Delivery Systems (LBDDS), including Self-Microemulsifying Drug Delivery Systems (SMEDDS), enhance solubility through lipid solubilization mechanisms. Other emerging strategies include co-crystals, which modify the drug’s crystalline structure to improve solubility, and mesoporous silica materials that offer high surface area and controlled release properties. These technologies are gaining traction in the pharmaceutical industry due to their effectiveness and scalability. This review aims to critically evaluate these modern approaches, focusing on their mechanisms, manufacturing feasibility, and current adoption trends over the past decade.