An accurate assessment of evapotranspiration (ET) is crucially needed at the basin scale for studying the hydrological processes and water balance especially from upstream to downstream. In the mountains, this term is poorly understood because of various challenges, including the vegetation complexity, plant diversity, lack of available data and because the in situ direct measurement of ET is difficult in complex terrain. The main objective of this work was to investigate the potential of a Two-Source-Energy-Balance model (TSEB) driven by the Landsat and MODIS data for estimating ET over a complex mountain region. The complexity is associated with the type of the vegetation canopy as well as the changes in topography. For validating purposes, a large-aperture scintillometer (LAS) was set up over a heterogeneous transect of about 1.4 km to measure sensible (H) and latent heat (LE) fluxes. Additionally, two towers of eddy covariance (EC) systems were installed along the LAS transect. First, the model was tested at the local scale against the EC measurements using multi-scale remote sensing (MODIS and Landsat) inputs at the satellite overpasses. The obtained averaged values of the root mean square error (RMSE) and correlation coefficient (R) were about 72.4 Wm−2 and 0.79 and 82.0 Wm−2 and 0.52 for Landsat and MODIS data, respectively. Secondly, the potential of the TSEB model for evaluating the latent heat fluxes at large scale was investigated by aggregating the derived parameters from both satellites based on the LAS footprint. As for the local scale, the comparison of the latent heat fluxes simulated by TSEB driven by Landsat data performed well against those measured by the LAS (R = 0.69, RMSE = 68.0 Wm−2), while slightly more scattering was observed when MODIS products were used (R = 0.38, RMSE = 99.8 Wm−2). Based on the obtained results, it can be concluded that (1) the TSEB model can be fairly used to estimate the evapotranspiration over the mountain regions; and (2) medium- to high-resolution inputs are a better option than coarse-resolution products for describing this kind of complex terrain.