Amidst increasing global connectivity and accelerating global change, the global security framework has become insufficient, contributing to a crippling dysfunctionality in international cooperation. The current security framework, focused almost exclusively on a narrow notion of military security, is insufficient to address escalating ‘threats without enemy,’ such as climate change, biodiversity loss, and pollution, which increasingly endanger the lives and dignity of all populations. This policy brief recommends a global social-ecological security framework, rooted in the science informed understanding of social and biophysical realities, to address the evolving needs and challenges of the 21st century. Our recommendations to operationalise this paradigm include: a reinvigorated commitment to multilateralism and peace as a pre-requisite; public participation in shaping the new inclusive international governance framework; development aid and green finance as key levers; a focus on building resilience (especially food security); and, strengthening anticipation of and response to interconnected global shocks. We propose a G20-initiated formation of a high-level working group to catalyse the creation of this new framework. Such a process must involve relevant stakeholders, leveraging new possibilities afforded by technological tools (such as AI). Implementing this ambitious agenda will be challenging, but continuing on a business as- usual trajectory is a ‘lose-lose’ spiral likely to trigger social and ecological crises. Bold leadership from the G20 is needed more than ever to reinvent multilateralism and thus ensure sustainable well-being for all.