Pharmaceutical products have been continuously evolving in the field of ophthalmology to address unmet needs of the patients. This has resulted in increasing reliance on dosage forms like emulsions, gels, ointments, and implants, often referred to as complex ophthalmics, owing to the difficulty in their chemistry, manufacturing and quality control. Converting complex ophthalmic products into generic versions is imperative to expand access to these advanced therapies across all segments of society. However, reverse engineering is often riddled with scientific challenges, which require investment of time and money. This chapter scrutinizes reverse engineering in complex ophthalmic drug products, specifying key methodologies crucial for their development and assessment. We begin with deformulation, exploring the systematic breakdown of formulations to identify their components. Following this, in vitro comparative characterization studies are discussed, which are critical for assessing the physicochemical properties of ophthalmic products comparative to reference formulations. Special emphasis is laid on in vitro release testing as a decisive component for assessing drug release rates and potential ocular bioavailability. The importance of clinical endpoint studies is also captured, signifying how these trials estimate the effectiveness and safety of generic formulations in real-world scenario vis-à-vis the already approved innovator product. The chapter also briefly discusses physiologically based pharmacokinetic (PBPK) models, which envisage drug pharmacokinetic behaviour based on its physicochemical properties and the dosage form in which it is administered, allowing for feasible prediction of absorption and action. This all-inclusive overview aims to elucidate the reverse engineering processes, emphasizing challenges and innovations in ophthalmic drug development and tries to provide a deeper understanding of this critical field.