Background: This study identifies differences in socio-cognitive factors as they relate to the intention to smoke among boys and girls living in high socioeconomic status (HSES) and low socioeconomic status (LSES) neighborhoods. Methods: A total of 1,643 children (aged 10-12 years) completed a web-based questionnaire assessing their intention, attitude, social influences, and self-efficacy toward smoking at baseline and at one year follow-up. Logistic regression analyses were conducted to examine the relations between intention and predictor variables (i.e. attitude, social influence, and self-efficacy). Three-way interaction terms were added to the first analysis to examine potential interactions of gender, socioeconomic status and predictor variables. A 3-way interaction effect was present, and therefore subgroup analyses for HSES and LSES boys and girls were warranted. Results: The results indicated that positive attitudes toward smoking were related to the intention to smoke among HSES boys, whereas HSES girls had higher intentions to smoke if they perceived fewer disadvantages of smoking (OR: 0.42; 95 % CI: 0.22-0.82). The intention to smoke among LSES boys was predicted by perceived social norms (OR: 0.49; 95 % CI: 0.25-0.93); in LSES girls, the smoking behavior of people in their environment was most strongly related to their smoking intention (OR: 5.55; 95 % CI: 2.81-10.93). Conclusions: To prevent youth smoking, HSES boys and girls may benefit from interventions that address attitudes. Boys from an LSES neighborhood may profit from smoking prevention interventions that target social norms, while LSES girls may benefit from strategies aimed at resisting the influence of smokers in their environment.