On 3 June 2018, Fuego volcano experienced a VEI = 3 eruption, which produced a pyroclastic density current (PDC) that devastated the La Réunion resort and the community of Los Lotes, resulting in over 100 deaths. To evaluate the potential hazard to the population centers surrounding Fuego associated with future PDC emplacement, we used an integrated remote sensing and flow modeling-based approach. The predominate PDC travel direction over the past 15 years was investigated using thermal infrared (TIR) data from the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) instrument validated with ground reports from the National Institute of Seismology, Volcanology, Meteorology, and Hydrology (INSIVUMEH), the government agency responsible for monitoring. Two different ASTER-derived digital elevation model (DEM) products with varying levels of noise were also used to assess the uncertainty in the VolcFlow model results. Our findings indicate that the recent historical PDC travel direction is dominantly toward the south and southwest. Population centers in this region of Fuego that are within ~2 km of one of the volcano’s radial barrancas are at the highest risk during future large eruptions that produce PDCs. The ASTER global DEM (GDEM) product has the least random noise and where used with the VolcFlow model, had a significant improvement on its accuracy. Results produced longer flow runout distances and therefore better conveys a more accurate perception of risk. Different PDC volumes were then modeled using the GDEM and VolcFlow to determine potential inundation areas in relation to local communities.