Tourism is a key driver of global socio-economic progress. However, its sustainability is at risk from multiple shocks and hazards that threaten livelihoods. Surprisingly little is known about the complex drivers of destination vulnerability, leading to the creation and application of ineffective resilience-building solutions. The paper presents the Destination Sustainability Framework (DSF) designed to assess destination vulnerability and resilience, and support successful resilience-building initiatives. Holistic in nature, the DSF comprises: (1) the shock(s) or stressor(s); (2) the interconnected dimensions of vulnerability - exposure, sensitivity, and system adaptiveness; (3) the dynamic feedback loops that express the multiple outcomes of actions taken (or not); (4) the contextualised root causes that shape destinations and their characteristics; (5) the various spatial scales; and (6) multiple timeframes within which social-ecological change occurs. This innovative framework is significant because it's the first framework to chart the complex manifestation of vulnerability and resilience in tourism destinations. Further, it brings tourism sustainability research in line with wider debates on achieving sustainability within the dynamic coupled human-environment system, doing so through the inclusion of insights from contemporary systems approaches, including chaos-complexity theory, vulnerability approaches, sustainability science, resilience thinking, along with the geographies of scale, place and time.