The study of nonlinear higher-order differential equations presents significant challenges in terms of existence and uniqueness of solutions. This paper explores novel approaches to addressing these challenges, focusing on recent advancements and methodologies that offer new perspectives on these classical problems. We investigate advanced techniques including topological methods, functional analysis, and computational approaches to enhance our understanding of existence and uniqueness in nonlinear higher-order differential equations. By reviewing the latest literature and integrating new findings, this paper aims to provide a comprehensive overview of current research trends and future directions in this area.