Large felids including Bengal tigers (Panthera tigris tigris), Indochinese leopards (Panthera pardus delacouri), and Mainland clouded leopards Neofelis nebulosa), face imminent threats in Southeast Asia due to overexploitation, habitat destruction, and climate change impacts. The Chindwin River Basin (CRB), a critical biodiversity hotspot in Myanmar has witnessed a decline in the populations of these big cats, attributed to deforestation, habitat loss, and illegal wildlife trade. There is a crucial research gap regarding climate change and land use change impacts on the distribution of large felids in the CRB. The objective of this study is to assess the influences of climate and land use alterations on the distribution of large felids in the Chindwin River Basin (CRB) of Myanmar. Specifically, we aim to examine habitat suitability, identify key environmental variables influencing felid distribution, and project future changes in habitat suitability under different climate and land use scenarios. To achieve this objective, we used presence-only GIS points of three felid species which were collected through extensive camera trap surveys between 2013 and 2018 in critical areas of the CRB, including the Hukaung Valley Wildlife Sanctuary, Htamanthi Wildlife Sanctuary, Alaungdaw Kathapa National Park, and Hphonkanrazi Wildlife Sanctuary. For the environmental variables, we incorporated altitude, slope, aspect, land cover types, and bioclimatic data. Ten algorithms and an ensemble modeling approach were employed to develop Species Distribution Models (SDMs) for the three felid species. Remote sensing and Geographical Information Systems were utilized to evaluate land use changes, and future land use scenarios were projected using supervised classification and cellular automata models. Our study reveals that suitable habitats for large felids in the CRB are not uniformly distributed, with protected areas covering a significant portion (57%) but crucial areas outside protected areas being necessary for species survival. Distribution patterns are influenced by environmental variables, including elevation, slope, land cover types, and human-related activities. The intricate relationship with rivers highlights the necessity for targeted conservation measures along riparian zones. Climate variables, such as temperature and precipitation fluctuations, also significantly influence felid distribution. Future projections indicate a general trend of decreasing habitat suitability for large felids under various climate and land use scenarios, emphasizing the urgent need for proactive conservation actions to mitigate habitat loss and species decline in the region.