Protected Areas (PAs) are vital tools for biodiversity conservation, yet climate poses a long-term threat to their effectiveness. Climate change can displace species from PAs or make them unsuitable. Among the most climate-threatened organisms are the amphibians, a group also affected by data limitations that ultimately mask their true vulnerability. Amphibians’ dependence on water highlights the wetlands’ vital role for amphibian conservation. The world's largest continuous tropical wetland is situated along the borders of Brazil, Bolivia, and Paraguay, the Pantanal and surroundings, where, 4% of 76 amphibian species are threatened, while 15% lack sufficient data for conservation assessments. We used Ensemble of Small Models to derive information on amphibian richness and composition in the Pantanal and surroundings, and applied null models to evaluate the current PA network’s effectiveness in protecting amphibians under future climate scenarios. Additionally, we used a systematic conservation planning algorithm to identify priority areas for PA network expansion. Our findings show that by 2080, over 90% of amphibian species are projected to lose suitable habitat, with 99% of amphibian assemblages facing climate-driven species loss. Although the existing PA network was relatively ineffective in preserving the amphibian’ richness, 20% of PAs are expected to shelter more species than expected by chance in the future. Notably, highlands exhibited pronounced changes in amphibian biodiversity and were recovered as priority areas for PA network expansion, particularly in the northern and southeastern boundaries of the Upper Paraguay River Basin, where Pantanal is included. Our research underscores the urgency of establishing new PAs to safeguard amphibian biodiversity.