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As Gavi embarks on its next strategic phase, “Gavi 6.0,” it faces multiple challenges: shifting donor priorities, rising costs of new vaccines, incomplete vaccine coverage, and economic constraints in supported countries. Additionally, health ministries face increasing pressures related to universal health coverage, complex disease burdens, and fragmented aid systems. This paper proposes that Gavi’s transition approach would benefit from adopting a New Compact underpinned by a marginal aid framework. The New Compact is based on three pillars that reflect a shared responsibility between a country and its donors: (1) evidence-informed, locally led prioritization; (2) domestic-first resource allocation with donor support for marginally cost-effective interventions; and (3) consolidated supplementary aid. We suggest five policy shifts for Gavi to enhance the New Compact’s effectiveness: focusing country financing on high-priority vaccines while using Gavi funds at the margins; ensuring comprehensive coverage for underserved populations; improving donor coordination; adapting pooled procurement; and strengthening market shaping through value-based commitments. We conclude with recommendations for Gavi’s transition, emphasizing the need for strategic dialogue and adaptive policies to align with the New Compact and achieve sustainable vaccination outcomes.