This review explores the advancements in green synthesis methodologies, focusing on the utilization of bio-assisted sources and benign solvents for the production of pharmaceutical nanoparticles. We discuss the significance of solvent systems in synthesis processes and highlight water as an ideal and accessible solvent. Various examples of nanoparticle synthesis in aqueous media are presented, including gold and silver nanoparticles produced via the emerging field of “green” synthesis, which encompasses routes utilizing water as a solvent system and natural sources/extracts as primary components. Notably, ionic liquids are discussed as promising solvents for nanoparticle synthesis, offering unique advantages such as tunable properties and broad temperature ranges. Furthermore, the potential of supercritical fluids, particularly carbon dioxide and water, as solvent systems for nanoparticle synthesis is explored. Nanoparticles have numerous uses in the pharmaceutical and medical industries. We hope to shed light on environmentally acceptable and sustainable methods for synthesizing nanoparticles with this thorough review