Using a real-time Green’s functions formalism, we investigate the influence of depletion charge scattering on the room temperature mobility in scaled silicon metal-oxide-semiconductor field-effect transistors and low-temperature transport in In0.4Al0.6As-In0.4Ga0.6As modulation doped heterostructures. Our simulation results suggest that depletion charge scattering, which is usually ignored, has considerable impact on the electron transport in silicon inversion layers near the threshold gate voltage, even at room temperature. We also find that the weighting coefficients a and b (for the inversion and depletion charge densities) strongly depend on the substrate doping and deviate from that reported in the literature. In the case of modulation doped heterostructures, the low-temperature mobility is limited by alloy and Coulomb scattering. Intersubband scattering considerably affects the broadening of the states which, in turn, leads to mobility reduction.