Aerosol and meteorological remote sensing data could be used to assess the distribution of urban and regional fine particulate matter (PM2.5), especially in locations where there are few or no ground-based observations, such as Latin America. The objective of this study is to evaluate the ability of Modern-Era Retrospective Analysis for Research and Application, version 2 (MERRA-2) aerosol components to represent PM2.5 ground concentrations and to develop and validate an ensemble neural network (ENN) model that uses MERRA-2 aerosol and meteorology products to estimate the monthly average of PM2.5 ground concentrations in the Monterrey Metropolitan Area (MMA), which is the main urban area in Northeastern Mexico (NEM). The project involves the application of the ENN model to a regional domain that includes not only the MMA but also other municipalities in NEM in the period from January 2010 to December 2014. Aerosol optical depth (AOD), temperature, relative humidity, dust PM2.5, sea salt PM2.5, black carbon (BC), organic carbon (OC), and sulfate (SO42−) reanalysis data were identified as factors that significantly influenced PM2.5 concentrations. The ENN estimated a PM2.5 monthly mean of 25.62 μg m−3 during the entire period. The results of the comparison between the ENN and ground measurements were as follows: correlation coefficient R ~ 0.90; root mean square error = 1.81 μg m−3; mean absolute error = 1.31 μg m−3. Overall, the PM2.5 levels were higher in winter and spring. The highest PM2.5 levels were located in the MMA, which is the major source of air pollution throughout this area. The estimated data indicated that PM2.5 was not distributed uniformly throughout the region but varied both spatially and temporally. These results led to the conclusion that the magnitude of air pollution varies among seasons and regions, and it is correlated with meteorological factors. The methodology developed in this study could be used to identify new monitoring sites and address information gaps.