Although highly relevant to the elimination of artemisinin-resistant Plasmodium falciparum, the entomological determinants of malaria transmission remain poorly described in the Greater Mekong Sub-region. As part of a pilot study on targeted malaria elimination, detailed entomological surveys were conducted in four villages for 24 months. We have demonstrated that the submicroscopic reservoir of asymptomatic malaria infections contributes to the transmission and that targeted mass drug administration is efficient in interrupting malaria transmission to the vectors. In addition, our data confirm previous observations that impregnated mosquito bed-nets have only a marginal impact on malaria in this area. Therefore, a drastic shift in vector-control intervention is required.