The International Network for the Demographic Evaluation of Populations and their Health (INDEPTH) has produced reliable longitudinal data about the lives of people in low- and middle-income countries (LMICs) through a global network of health and demographic surveillance system (HDSS) sites. Since reliable demographic data are scarce across many LMICs, we examine the environmental and socioeconomic (ES) similarities between existing HDSS sites and the rest of the LMICs. The HDSS sites were hierarchically grouped by the similarity of their ES conditions to quantify the ES variability between sites. The entire Africa and Asia region was classified to identify which regions were most similar to existing sites, based on available ES data. Results show that the current INDEPTH network architecture does a good job in representing ES conditions, but that great heterogeneities exist, even within individual countries. The results provide valuable information in determining the confidence with which relationships derived from present HDSS sites can be broadly extended to other areas, and to highlight areas where the new HDSS sites would improve significantly the ES coverage of the network.