The variability in the relation between brightness temperature and rain intensity is due mostly to uncertainties in horizontal and vertical rainfall structures within a satellite’s field of view (FOV). Because the variability associated with the uncertainties affects microwave rainfall estimates significantly, it is crucial to understand the radiometric response to the high variability of rainfall structures. In this study, brightness temperatures and rainfall profiles measured from the Tropical Rainfall Measuring Mission (TRMM) Microwave Imager (TMI) and the Precipitation Radar (PR) are examined to quantify the effect of inhomogeneous characteristics of rainfall within the TMI FOVs. This purely observational approach will provide insight into the retrieval errors that supplement detail cloud modeling based on radiative transfer calculations. We show that the horizontal inhomogeneity of rainfall is related to its vertical structure and hence the combined effect contributes to increasing the uncertainty in the retrievals. Uncertainty due to rainfall inhomogeneity is significant enough to weaken the microwave radiometric signatures. We found significant regional differences in the radiometric response between two climate regimes, the East and West Pacific. In the West Pacific, which is characterized by greater non-uniformity of rainfall, the unique radiometric signature is degraded significantly at the low frequencies where emission dominates. This results in higher nonlinearity in the physical connection. It is therefore suggested that retrieval biases are dependent on climate regimes where different horizontal and vertical precipitation structures exist.