This study examined the role of supportive relationships (i.e., family, teacher, and peer) and agency (i.e., self-efficacy, motivation, and goal-setting orientation) on three outcomes: academic grades, distress, and career decidedness. Data from 588 middle school youth from Northern (N = 322) and Southern (N = 266) Italy were analyzed using path modeling. Results indicated that across gender and region, agency was consistently related to academic grades and career decidedness. However, the role of supportive relationships was found to differ across gender and region. For both boys from Northern Italy and girls from Southern Italy, the impact of family support on academic grades and career decidedness was mediated by agency. For girls from Northern Italy, family support related directly to academic grades and career decidedness. Implications for practice were described.