To achieve the ambitious goals of the UN Decade on Ecosystem Restoration, restoration frameworks should embrace the diversity of ecosystems found on Earth, including open-canopy ecosystems, which have been largely overlooked. Considering the paucity of scientific foundations promoting restoration science, policy, and practice for open tropical ecosystems, we provide overarching guidelines to restore the campo rupestre, a Neotropical, open megadiverse grassland that has been increasingly threatened by multiple human activities, especially mining. Restoration techniques for tropical grasslands are still at its infancy, and attempts to restore campo rupestre have had, so far, low to moderate success, highlighting the need for a tailored restoration framework. In a scenario of increasing degradation and scarcity of on-site restoration experiments, we propose 10 principles to improve our ability to plan, implement, and monitor restoration in campo rupestre: (1) include socioeconomic dimensions, (2) implement active restoration, (3) keep low soil fertility, (4) restore disturbance regimes, (5) address genetic structure and adaptation potential, (6) restore geographically restricted and specialized ecological interactions, (7) incorporate functional approaches, (8) use seed-based restoration strategies to enhance biodiversity, (9) translocation is inevitable, and (10) long-term monitoring is mandatory. Our principles represent the best available evidence to support better science and practice for the restoration of campo rupestre and, to some extent, can be useful for other megadiverse, fire-prone, and nutrient-poor ecosystems.