This study examined the role of culture and personality on the career decision self-efficacy of 338 Latino seventh-grade public middle school students. Specifically, we examined the role of acculturation, enculturation, ethnic identity, and conscientiousness on career decision self-efficacy. Findings indicated Latina girls were more acculturated and enculturated than Latino boys. For Latino boys and Latina girls, respectively, 34% and 25% of the variance in career decision self-efficacy was accounted for by the predictors. Acculturation, ethnic identity, and conscientiousness significantly predicted career decision self-efficacy for girls. For boys, however, only ethnic identity and conscientiousness were unique significant predictors. As expected, enculturation did not significantly predict career decision self-efficacy for either boys or girls. An interaction effect between acculturation and enculturation did not significantly predict career decision self-efficacy for boys or girls. Implications for practice and future research are discussed.