The approval of generic medicines plays a crucial role in enhancing healthcare accessibility, reducing treatment costs, and supporting sustainable public health systems worldwide. However, the regulatory expectations for generic drug dossiers differ significantly across regions, influencing development timelines, compliance burden, and market entry strategies. This review provides a comprehensive comparative analysis of dossier submission requirements for generic drug approval in India and the European Union (EU), with a focus on key regulatory components, harmonization efforts, existing challenges, and future directions. The paper examines critical modules of the Common Technical Document (CTD), including quality, nonclinical, and clinical/bioequivalence data, highlighting similarities and distinctions between the Central Drugs Standard Control Organization (CDSCO) in India and the European Medicines Agency (EMA) in the EU. Special attention is given to variations in bioequivalence study expectations, stability testing protocols, reference product selection, GMP compliance, data integrity standards, and timelines for review and approval. Despite ongoing global efforts toward harmonization—supported by ICH guidelines and WHO recommendations—substantial gaps persist. These differences often impact regulatory predictability for pharmaceutical manufacturers and can delay patient access to affordable generics. The review identifies major regulatory challenges such as procedural complexity, evolving documentation requirements, and country-specific technical barriers. Finally, the paper proposes future pathways for improving convergence between Indian and EU regulatory frameworks, emphasizing risk-based evaluation, digital submission platforms, enhanced reliance pathways, and strengthened global collaboration. Such harmonization has the potential to streamline generic drug development, promote regulatory efficiency, and ultimately improve global medicine availability.