The vertical transport of nonequilibrium charge carriers through semiconductor heterostructures has led to milestones in electronics with the development of the hot-electron transistor. Recently, significant advances have been made with atomically sharp heterostructures implementing various two-dimensional materials. Although graphene-base hot-electron transistors show great promise for electronic switching at high frequencies, they are limited by their low current gain. Here we show that, by choosing MoS2 and HfO2 for the filter barrier interface and using a noncrystalline semiconductor such as ITO for the collector, we can achieve an unprecedentedly high-current gain (α ∼ 0.95) in our hot-electron transistors operating at room temperature. Furthermore, the current gain can be tuned over 2 orders of magnitude with the collector-base voltage albeit this feature currently presents a drawback in the transistor performance metrics such as poor output resistance and poor intrinsic voltage gain. We anticipate our transistors will pave the way toward the realization of novel flexible 2D material-based high-density, low-energy, and high-frequency hot-carrier electronic applications. © 2015 American Chemical Society.