The advent of the Anthropocene underscores the need to develop and implement transformative governance strategies that safeguard the Earth's life-support systems, most critically at the ocean–land interface — the Margin. The seaward realm of the Margin is the new frontier for resource exploitation and colonization to meet the needs of coastal nations and humanity overall. Here, we spotlight the pivotal role of the Margin for planetary resilience and sustainability, highlight priority issues, and outline a research strategy which aims to: (a) better understand Margin social-ecological systems; (b) guide sustainable development of Margin resources; (c) design governance regimes to reverse unsustainable practices; (d) facilitate equitable sharing of Margin resources; and (e) evaluate alternative research approaches and partnerships that address major Margin challenges.