Despite considerable progress toward malaria elimination in Myanmar, challenges remain owing to the persistence of complex focal transmission reservoirs. Nearly all remaining infections are clinically silent, rendering them invisible to routine monitoring. Moreover, limited knowledge of population distributions and human activity on the landscape in remote regions of Myanmar hinders the development of targeted malaria elimination approaches, as advocated by the World Health Organization (WHO). This is especially true for Ann Township, a remote region of Myanmar with a high malaria burden, where a comprehensive understanding of local exposure, which includes the characterization of environmental settings and land use activities, is crucial to developing successful malaria elimination strategies. In this dissertation, I present an interdisciplinary approach that combines satellite earth observations with two separate on-the-ground surveys to assess human exposure to malaria at multiple scales. First, I mapped rural settlements using a fusion of Landsat imagery and multi-temporal auxiliary data sensitive to human activity patterns with a classification accuracy of 93.1%. A satellite data-based map of land cover and land use was then used to assess landscape-scale malaria exposure as a function of environmental settings for a subset of ten villages where a malaria prevalence survey was carried out. While multiple significant associations were discovered, the relationship found between malaria exposure and satellite-measured village forest cover was the most significant. Finally, a separate detailed survey that explored a variety of land use activities, including their frequency and duration along with testing for clinical or subclinical malaria, was used to identify and quantify factors promoting an individual’s likelihood of malaria infection regardless of the environmental settings. This analysis established strong associations between malaria and individual land use activities that bring respondents into direct contact with forested areas. These results highlight that the current Myanmar malaria elimination strategies, which focus on prevention from within the home (i.e., bednets and indoor spraying), are no longer sufficient to remove remaining malaria reservoirs in the country. A paradigm shift in malaria elimination strategies towards targeted interventions that can disrupt malaria transmission in the settings where the exposure occurs are critical to achieving country-wide malaria elimination.