A framework is proposed for understanding the efficacy of the microwave radiative transfer model (RTM) of soil moisture with different support scales, seasonality (time), hydroclimates, and aggregation (scaling) methods. In this paper, the sensitivity of brightness temperature TB (H- and V-polarization) to physical variables (soil moisture, soil texture, surface roughness, surface temperature, and vegetation characteristics) is studied. Our results indicate that the sensitivity of brightness temperature (V- or H-polarization) is determined by the upscaling method and heterogeneity observed in the physical variables. Under higher heterogeneity, the TB sensitivity to vegetation and roughness followed a logarithmic function with an increasing support scale, while an exponential function is followed under lower heterogeneity. Surface temperature always followed an exponential function under all conditions. The sensitivity of TB at H- or V- polarization to soil and vegetation characteristics varied with the spatial scale (extent and support) and the amount of biomass observed. Thus, choosing an H- or V-polarization algorithm for soil moisture retrieval is a tradeoff between support scales, and land surface heterogeneity. For largely undisturbed natural environments such as SGP97 and SMEX04, the sensitivity of TB to variables remains nearly uniform and is not influenced by extent, support scales, or an upscaling method. On the contrary, for anthropogenically-manipulated environments such as SMEX02 and SMAPVEX12, the sensitivity to variables is highly influenced by the distribution of land surface heterogeneity and upscaling methods.