Background Shortages of essential medicines impact patient safety and raise the costs of medicines to consumers and governments. Ongoing medicine shortages have become a critical issue that threaten global access to medicines. Objective The aim of this study was to explore key stakeholders' perspectives on the challenges surrounding management and supply of essential medicines. Setting Western Pacific, Asia, Europe, North America, and Africa. Methods In-depth, semi-structured interviews with 47 participants were conducted across seven stakeholder groups globally. Stakeholders included government, academics, consumer groups, non-profit organisations, hospital healthcare providers, manufacturers, and wholesaler/distributors. A grounded theory approach was applied to qualitative analysis. Main outcome measure Stakeholders' perspectives on the challenges surrounding management and supply of essential medicines. Results This study showed that supporting consumer demand for a wide range of therapeutic products required increased resources and coordination. Four main themes were identified: (1) consumer demand for a wide range of individual therapeutic needs cannot be sustained by the supply chain; (2) there lacked a coordinated approach to manage medicine shortages throughout the supply chain; (3) there were gaps in communication throughout the continuum of the supply chain; and (4) both international and local disruptions contributed to vulnerabilities in the supply chain. Conclusion Prioritisation of supply, logistics, and budget decisions around essential medicines need to be clearly coordinated between stakeholders to mitigate medicine shortages. Financial structures should include resilience planning to support fair and equitable access to medicines that meet consumer needs.