Environmental exposures and their health impacts can vary substantially between urban and rural areas. However, different methods for classifying these areas could lead to inconsistencies in environmental exposure and health studies, which are often overlooked. We constructed different urban/rural classification systems based on multiple population-based (e.g., total population, population density, and commuting) and builtenvironment-based (e.g., nighttime light intensity, building density, road density, distance to urban centers, point of interest density, and urban area coverage) indicators and various classification schemes. These classification systems were applied to Virginia and West Virginia, United States. We compared differences in urban/ rural spatial patterns, demographic compositions, and exposures of particulate matter (PM 2.5 ), greenspace, and land surface temperature using these urban/rural classification systems to understand their impacts on environmental exposure and health research. Our findings reveal clear differences in spatial patterns and demographic compositions across various systems. We also observed that different systems can lead to changes in the magnitude and direction of urban/rural disparities in environmental exposure assessment. Addressing the complexities in delineating urbanicity and rurality may include careful consideration of classification systems to reflect those aspects of urbanicity and rurality that are relevant to the research question or the use of multiple, complementary systems.