Background: Inadequate administrative health data, suboptimal public health infrastructure, rapid and unplanned urbanization, environmental degradation, and poor penetration of information technology make the tracking of health and well-being of populations and their social determinants in the developing countries challenging. Technology-integrated comprehensive surveillance platforms have the potential to overcome these gaps. Objective: This paper provides methodological insights into establishing a geographic information system (GIS)-integrated, comprehensive surveillance platform in rural North India, a resource-constrained setting. Methods: The International Clinical Epidemiology Network Trust International established a comprehensive SOMAARTH Demographic, Development, and Environmental Surveillance Site (DDESS) in rural Palwal, a district in Haryana, North India. The surveillance platform evolved by adopting four major steps: (1) site preparation, (2) data construction, (3) data quality assurance, and (4) data update and maintenance system. Arc GIS 10.3 and QGIS 2.14 software were employed for geospatial data construction. Surveillance data architecture was built upon the geospatial land parcel datasets. Dedicated software (SOMAARTH-1) was developed for handling high volume of longitudinal datasets. The built infrastructure data pertaining to land use, water bodies, roads, railways, community trails, landmarks, water, sanitation and food environment, weather and air quality, and demographic characteristics were constructed in a relational manner. Results: The comprehensive surveillance platform encompassed a population of 0.2 million individuals residing in 51 villages over a land mass of 251.7 sq km having 32,662 households and 19,260 nonresidential features (cattle shed, shops, health, education, banking, religious institutions, etc). All land parcels were assigned georeferenced location identification numbers to enable space and time monitoring. Subdivision of villages into sectors helped identify socially homogenous community clusters (418/676, 61.8%, sectors). Water and hygiene parameters of the whole area were mapped on the GIS platform and quantified. Risk of physical exposure to harmful environment (poor water and sanitation indicators) was significantly associated with the caste of individual household (P=.001), and the path was mediated through the socioeconomic status and density of waste spots (liquid and solid) of the sector in which these households were located. Ground-truthing for ascertaining the land parcel level accuracies, community involvement in mapping exercise, and identification of small habitations not recorded in the administrative data were key learnings. Conclusions: The SOMAARTH DDESS experience allowed us to document and explore dynamic relationships, associations, and pathways across multiple levels of the system (ie, individual, household, neighborhood, and village) through a geospatial interface. This could be used for characterization and monitoring of a wide range of proximal and distal determinants of health.