Global fulfillment networks that are the backbone of international supply chains are increasingly dealing with unprecedented security challenges in an era characterized by advanced cyber-attacks, data breaches and increasing regulatory compliance issues. As digital ecosystems become more distributed and the wider business environment starts to converge with it, traditional perimeter-based security frameworks are increasingly ineffective, in that they require more dynamic solutions that are identity-based, in order to secure the assets and maintain business continuity. The present-day condition of unresolved threats to global fulfillment operations is a critical issue and the article will focus on the strategic mechanism of removing vulnerabilities at the scale provided by Zero-Trust Security enhanced by Multi-Factor Authentication (MFA). The strategy will focus on synergies between the Zero-Trust concepts continuous verification, least-privilege access, micro-segmentation and scalable MFA rollout which altogether would turn enterprise access management into a proactive and adaptive defense. The analysis identifies the practicality of MFA implementation in the global environment, and the practicality of metrics-driven approach to evaluate the availability, security resilience and cost efficiency. Through a vulnerabilities and mitigation strategy framework, the paper shows how Zero-Trust and MFA work together to deal with cross border exposure to data, identity compromise and internal risks in the fulfillment network. This work will provide a contribution to the field because it will provide a metrics-based, enterprise aligned model that allows organizations to strike the right balance between security and operational flexibility requirements. Governance imperatives, leadership opportunities, and future direction of passwordless and AI-based authentication were all noted in the article, bringing Zero-Trust with MFA as a strategic enabler, as well as a technological requirement of a global fulfillment ecosystems.