This book provides a comprehensive and systematic framework for digital twin-driven manufacturing systems in the era of Industry 5.0. As the demand for human-centric, resilient, and sustainable manufacturing continues to grow, Digital Twin technology is emerging as a key enabler of end-to-end digitalization across the entire product manufacturing lifecycle. Yet, despite its potential, industrial adoption still faces significant challenges, including fragmented data, limited interoperability, insufficient real-time optimization, and concerns surrounding data security. To address these gaps, the book clarifies core concepts and defining characteristics of digital twin-driven systems, introduces essential enabling technologies, and presents practical methodologies for system design and implementation. It also explores advanced and emerging topics such as cross-X manufacturing and biotwins, while discussing future opportunities shaped by the Industry 5.0 paradigm. By integrating recent research outcomes with real-world case studies, the book serves as both a rigorous academic reference and a practical guide for researchers, engineers, and industry professionals.