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Identifying protected areas most susceptible to climate change and deforestation represents critical information for determining conservation investments. Development of effective landscape interventions is required to ensure the preservation and protection of these areas essential to ecosystem service provision, provide high biodiversity value, and serve a critical habitat connectivity role. We identified vulnerable protected areas in the humid tropical forest biome using climate metrics for 2050 and future deforestation risk for 2024 modeled from historical deforestation and global drivers of deforestation. Results show distinct continental and regional patterns of combined threats to protected areas. Eleven Mha (2%) of global humid tropical protected area was exposed to the highest combined threats and should be prioritized for investments in landscape interventions focused on adaptation to climate stressors. Global tropical protected area exposed to the lowest deforestation risk but highest climate risks totaled 135 Mha (26%). Thirty-five percent of South America’s protected area fell into this risk category and should be prioritized for increasing protected area size and connectivity to facilitate species movement. Global humid tropical protected area exposed to a combination of the lowest deforestation and lowest climate risks totaled 89 Mha (17%), and were disproportionately located in Africa (34%) and Asia (17%), indicating opportunities for low-risk conservation investments for improved connectivity to these potential climate refugia. This type of biome-scale, protected area analysis, combining both climate change and deforestation threats, is critical to informing policies and landscape interventions to maximize investments for environmental conservation and increase ecosystem resilience to climate change.