Nanocrystals represent an advanced approach to improve the solubility and bioavailability of drugs with poor aqueous solubility. Their formulation requires a well-structured optimization process that leverages techniques such as high-pressure homogenization, wet milling, and precipitation to achieve optimal particle size and stability. Enhancing drug solubility primarily depends on reducing particle size, modifying surface properties, and selecting appropriate stabilizers to facilitate dissolution and absorption. However, maintaining stability remains a challenge as drug nanocrystals are susceptible to aggregation, Ostwald ripening, and structural transformations over time. To counteract these issues, stabilization strategies such as polymeric coatings, lyophilization, and surfactant incorporation are employed to preserve their physicochemical properties and extend shelf life. This chapter emphasizes key optimization strategies, and solubility and stability considerations for drug nanocrystal formulations, which are essential for maximizing their therapeutic potential.