Malaria transmission has drastically reduced in several areas of the Greater Mekong Subregion (GMS), approaching the "final mile" towards elimination. With a shift from vector control towards the elimination of parasites from the human reservoir, the emergence and spread of multidrug resistant lineages has become a dominant concern. The study of the genomics of parasite populations helps us understand the underlying epidemiological mechanisms, characterize the resistant lineages, and discover the genetic drivers of resistance. Such knowledge about the rapidly changing parasite population can support rapid adaptive changes in policy, retaining drug efficacy while reducing parasite numbers. To produce the necessary impact, however, information must be delivered in a timely and actionable fashion to National Malaria Control Programmes (NMCPs) driving the elimination efforts. We present data from GenRe-Mekong, a regional project that conducts large-scale comprehensive genetic profiling of circulating parasite populations, providing public health authorities with rich information on markers of resistance to first-line treatments and alternative drugs, routes of gene flow within countries and across borders, hotspots of transmission, detection of recrudescence; and changes in population structure resulting from interventions. GenRe-Mekong operates in several GMS countries, in direct collaboration with NMCPs and public health facilities, as well as leading local and international research groups. As the project matures, it aims to transfer genomic technologies to endemic countries, and promote valuable collaborative data sharing between countries to achieve regional elimination.