The current paper compared the empirical structure of 280 variables from the 2016 wave of the Health and Retirement Study (N = 16,327) estimated using exploratory graph analysis with a theoretical structure based on 20 broad domains of intrinsic capacity, functional ability and environment, identified in the International Classification of Functioning, Disability and Health compendium. The results showed that a structure with 21 first-order factors had the best fit to the data (i.e., lowest total entropy fit value) for both the training and validation sample. A second-order exploratory graph analysis was applied on the interfactor correlation matrix and identified five second-order factors. The five-factor structure presented a better fit than the theoretical three-factor structure (approximately) representing intrinsic capacity, functional ability and environment. A close inspection of the network structure generated by analyzing the rotated network loadings of the 21 first-order factors revealed an interplay between cognition, mobility, need for help with daily activities, walking capacity, physical capacity, liver functioning, positive affect and perceived mastery, low perceived control, and depression/negative mood. Combined, our results can help guide future research by providing a framework for estimating the structure of multi-domain aging research as well as generating questions that can be addressed in future research.