While the association between residential socioeconomic environments and the use of globally common substances such as alcohol and tobacco has been well documented in Western countries, it remains little known about regionally important substances, such as areca nut in Asia. Objective: This study was aimed to develop residential environmental indicators in the context of Taiwan and examine their associations with areca nut use, in comparison to alcohol and tobacco use. Methods: Data were drawn from 13,392 adults across 168 townships in the 2014 National Survey on Substance Use in Taiwan. Residential socioeconomic environment variables were derived from the census and analyzed using factor analysis. Multilevel logistic regression models were used to examine the association of individual- and residential-level factors with the use of areca nut (use/nonuse), alcohol (harmful use, low-risk use, or nonuse), and tobacco (nicotine dependence, regular active use, or nonuse). Results: A three-factor structure of socioeconomic environments derived from 16 residential-level variables consisted of Rural Disadvantage, Affluence, and Family Fragmentation. Multilevel analyses showed that areca nut use was associated with both individual-level (male sex, age group 35-44 years, being divorced/widowed/separated, low educational attainment, and the occupational group of labors) and residential-level (Rural Disadvantaged and Family Fragmented) variables; such a profile was most similar to that of nicotine dependence. Conclusions: A three-factor structure could be derived for the residential-level socioeconomic environments in the Taiwanese context. Rural Disadvantaged and Family Fragmented were associated with areca nut use, which have implications for interventions targeted at the community level.