The rapid advancement of biotechnology has revolutionized the field of vaccine development, enabling the creation of more effective and safer vaccines. This review explores the historical progression of vaccine development, highlighting significant milestones and the shift from traditional methods to modern biotechnological approaches. It delves into various biotechnological techniques such as recombinant DNA technology, genetic engineering, synthetic biology, and protein engineering that have significantly enhanced vaccine production and formulation. The emergence of novel vaccine platforms, including mRNA, viral vector, DNA, and nanoparticle-based vaccines, is discussed with a focus on their development and clinical impact. Case studies, particularly the recent development of COVID-19 vaccines, illustrate the transformative role of biotechnology in responding to global health crises. The review also addresses the challenges and limitations inherent in biotechnological advancements, such as technical hurdles, regulatory issues, and ethical considerations. Additionally, it examines the impact of these innovations on vaccine safety, efficacy, and public health, and anticipates future trends in personalized and universal vaccines. Through this comprehensive analysis, the review underscores the pivotal role of biotechnology in the ongoing evolution of vaccine development and its profound implications for global health.