Aim: To identify Neotropical ecoregions experiencing compound environmental exposure to El Niño/La Niña-driven climate variability, deforestation trends and fire-induced forest loss. Location: Neotropical realm. Methods: We quantified historical exposure to ENSO-related climate variability by correlating the Oceanic Niño Index with four terrestrial climate variables (minimum and maximum temperatures, precipitation and Palmer drought severity index) for the period 1961–2021. Pixel-level correlations were aggregated into El Niño and La Niña exposure indices using entropy-weighting. Forest disturbance was characterized using cumulative forest loss, mean annual loss rate and fire-induced canopy loss derived from global remote-sensing datasets (2001–2023). Principal component analysis and K-means were used to classify ecoregions based on multi-variate exposure profiles. Results: Four clusters were identified across 150 forested ecoregions. ENSO-related climate exposure dominated regions from Central America to northern South America (27.3% of ecoregions), while deforestation (10.7%) and fire-induced forest loss (8.0%) characterized ecoregions primarily in the Amazon Basin and the Caribbean. Seven ecoregions, mainly in Colombia and Venezuela, exhibited consistently high exposure across climate variability, deforestation and fire-related disturbance: lowland moist forests (Catatumbo and Magdalena-Urabá), montane forests (Cordillera Oriental and Magdalena Valley) and dry forests (Apure-Villavicencio, Maracaibo and Patía). Main Conclusion: Our results highlighted clear patterns of compound exposure, identifying ecoregions where climatic variability may interact with ongoing land-use pressures. While exposure does not equate to ecological vulnerability, these findings provide a biogeographical foundation for prioritizing regions where sensitivity and adaptive capacity assessments are most urgently needed.