Malaria cases in Latin America reached ~1 million in 2017 and 2018, with 53% and 51% reported from Venezuela, respectively. In this study, we characterized the spatiotemporal dynamics of malaria transmission between 2007-2017 in southern Venezuela, the main endemic area of the country. We found that disease transmission was focal and more prevalent in the southeast of southern Venezuela where two persistent hotspots of Plasmodium vivax (76%) and P. falciparum (18%) linked to deforestation for illegal gold mining accounted for ~60% of the country-wide number of cases. Incidence has increased nearly tenfold in the last decade, showing an explosive epidemic growth due to a significant lack of disease control. We suggest that a source-sink pattern of Plasmodium sp.dispersal account for the re-emergence and progression of malaria transmission in the last 4 years across the country due to the internal migration of infected people to and from the hotspots and other malaria-prone ecosystems. We observe a similar pattern explaining the spillover of cases across international borders affecting neighboring countries. This study provides baseline epidemiological data and guidance for malaria control to further assess the dynamics of cross-border malaria, the role of asymptomatic carriers, drug-resistant evolution, and innovative control efforts in the Latin America region.