Climate change impact on species is commonly assessed by predicting species’ range change, a measure of a species’ extrinsic exposure. However, this is only one dimension of species’ vulnerability to climate change. Spatial arrangement of suitable habitats (e.g., fragmentation), their degree of protection or human disturbance, as well as species’ intrinsic sensitivity, such as climatic tolerances, are often neglected. Here, we consider components of species’ intrinsic sensitivity to climate change (climatic niche specialization and marginality) together with components of extrinsic exposure (changes in range extent, fragmentation, coverage of protected areas, and human footprint) to develop an integrated vulnerability index to climate change for world’s freshwater otters. As top freshwater predators, otters are among the most vulnerable mammals, with most species being threatened by habitat loss and degradation. All dimensions of climate change exposure were based on present and future predictions of species distributions. Annual mean temperature, mean diurnal temperature range, mean temperature of the wettest quarter, precipitation during the wettest quarter, and precipitation seasonality prove the most important variables for otters. All species are vulnerable to climate change, with global vulnerability index ranging from -0,19 for Lontra longicaudis to -36,9 for Aonyx congicus. However, we found that, for a given species, climate change can have both positive and negative effects on different components of extrinsic exposure, and that measures of species’ sensitivity are not necessarily congruent with measures of exposure. For instance, the range of all African species would be negatively affected by climate change, but their different sensitivity offers a more (Hydrictis maculicollis, Aonyx capensis) or less (Aonyx congicus) pessimistic perspective on their ability to cope with climate change. Also, highly sensitive species like the South-American Pteronura brasiliensis, Lontra provocax, and Lutra perspicillata might face no exposure to climate change. For the Asian Lutra sumatrana, climate change would instead lead to an increased, less fragmented, and more protected range extent, but the range extent would also be shifted into areas with higher human disturbances. Our study represents a balanced example of how to develop an index aimed at comparatively evaluating vulnerability to climate change of different species by combining different aspects of sensitivity and exposure, providing additional information on which to base more efficient conservation strategies.