The regulatory submission process has moved from paper dossiers to digital, data-driven, artificial intelligence (AI)-enabled reviews. This shift resolved the logistical and harmonisation challenges, thereby enabling faster reviews, accuracy, and increased efficiency. Even though regulatory submissions have been transforming over the last several decades, the primary philosophy continues to focus on patient centricity through benefit-risk assessment. Both sponsors and regulators have been exploring and adopting automation and AI tools to handle scale and improving submission quality. In the future, AI-enabled reviews could support human reviewers in regulatory decision-making by streamlining workflows and reducing the number of errors. Challenges remain around ethics, data privacy, harmonised standards, and explainability. There is a need for greater acceptance of the validated surrogate and digital endpoints, use of platform trials, and the expanded role of AI in triage.