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The global health landscape is undergoing a significant transformation as traditional frameworks of cooperation face fragmentation amid geopolitical tensions. Declining support from Western nations, exemplified by US withdrawal from the World Health Organization and cuts to programs like the President's Emergency Plan for AIDS Relief, has exposed the profound instability of an aid architecture built on colonial dependencies. The COVID-19 pandemic, marked by vaccine nationalism, was a stark litmus test of this systemic failure for low- and middle-income countries (LMICs). This commentary argues that the current geopolitical fragmentation, while a crisis, also presents a critical opportunity to dismantle colonial legacies and reimagine global health equity not as a donor-driven ideal, but as a practice of shared power and sovereignty. We first document the rise of alternative pathways, critically examining China's health diplomacy and India's pharmaceutical disruption, while highlighting robust, LMIC-led initiatives like the African Medicines Agency and local mRNA vaccine production in Rwanda and Thailand. In response to the fractured status quo, we then propose a new global health compact built on four interdependent pillars: (i) Epistemic Justice, valuing local knowledge systems; (ii) Structural Audacity in Financing, such as taxing multinational corporations for reparative funding; (iii) Governance for Agency, ceding decisive power to LMICs; and (iv) Open Knowledge and Innovation, by dismantling restrictive intellectual property regimes. Achieving this decolonized future requires concrete action from all stakeholders. We conclude with a blueprint urging high-income countries to cede power, LMICs to invest in local capacity, funders to provide untied financing, and researchers to practise equitable collaboration. This actionable agenda is the foundation for a truly equitable global health system capable of achieving Universal Health Coverage.