The drug delivery to the eye undergoes challenges because of its unique anatomical and typical physiological characteristics. The conventional methods which are delivered through oral and systemic routes often lead to significant side effects, so application through the topical route is the most efficient and suitable approach to ocular formulations. Nonetheless, because of the eye’s inherent shape, the retention of topical formulations decreases, leading to more frequent dosing, which can lead to undesirable side effects. To enhance the capacity for drug retention, a novel delivery system presents a promising strategy. However, the excipients and solvents could exhibit toxic effects. So, it is important to construct the safety profile in the initial steps by having a thorough understanding of the regulatory aspects and technical challenges. Various reports showed that the nanoformulation development by the quality by design (QbD) approach displayed a higher success rate by reducing the significant loss. It is a risk and knowledge-based systematic tool that ensures an understanding of the material and the process variables of final formulation. The key elements and design tools help in pre-defining and optimizing the final lead formulations with limited experimental trials. This approach focuses on improving the process quality which influences the manufacturing efficiency of the ophthalmic products.