<p>Poor oral bioavailability in most modern pharmaceuticals is primarily caused by poor aqueous solubility. Most NCEs (New Chemical Entities) and nearly 40% of drugs on the market fall into either Biopharmaceutical Classification System (BCS) class II or IV, both characterized by very poor aqueous solubility. This leads to a higher demand for techniques that improve solubility in water-based media. This study aims to compile and present a comprehensive and detailed assessment of cocrystals and nano-cocrystals. It emphasizes the importance of in-depth research into nano-cocrystals to gather more raw data, which will support the eventual translation of nano-cocrystals into clinical use and market approval. Cocrystal technology has been used to enhance various physicochemical parameters, including stability, solubility, and bioavailability. Nano-cocrystallization is a new emerging technique that combines the benefits of cocrystallization with nanosizing, resulting in cocrystals with improved physicochemical properties and increased surface area due to nanoscale particles. These methods not only enhance aqueous solubility but have also been shown to directly increase the dissolution rate and improve the dissolution profile of drug substances. A literature review was conducted using PubMed, Scopus, and patent databases. Cocrystals and multicomponent systems are discussed with an emphasis on their crystal structure, types and nature of bonds formed, and any significant variations or special characteristics are highlighted. This thorough review offers an overview of cocrystals and nano-cocrystals, outlining the cocrystallization process and various methods for formulation and characterization. It also covers the selection process for coformers, including new computational, AI, and machine learning techniques for screening. The review introduces nano-cocrystals, describing their synthesis methods and benefits. It discusses polymorphism in both cocrystals and nano-cocrystals, and compares cocrystals as a way to improve solubility. Additionally, it evaluates their different applications and clinical outcomes. The discussion points out that the limited research on nano-cocrystals hinders their translation into industrial and clinical use. In contrast, cocrystals, despite some barriers, have achieved notable commercial success.</p> Graphical Abstract <p></p>