This chapter explores the role of Entrepreneurial Orientation (EO) in enhancing supply chain resilience amidst sustainability challenges. EO, characterized by innovation, risk-taking, and proactivity, empowers organizations to develop adaptive and sustainable supply chains. The integration of advanced technologies like AI, IoT, and blockchain with EO facilitates real-time data insights, operational efficiency, and transparency. The chapter highlights the importance of circular economy models and social sustainability, and discusses the implications of evolving regulatory frameworks and collaborative ecosystems. By focusing on long-term value creation and leveraging collaborative approaches, organizations can address systemic sustainability issues and improve supply chain performance. The insights provided offer valuable guidance for future research and practical application in building resilient and sustainable supply chains.