In the Swiss education system, approximately 55% of adolescents are required to make their first vocational choice at the end of mandatory school. This can induce transitory or long-lasting career indecision that is recognized as being influenced by personal and contextual factors. The aim of this study is to analyze the relationships between career decision-making difficulties and the five-factor model of personality traits, parental support, and self-esteem in 448 Grade 9 Swiss adolescents. We then proceeded to test if these relationships vary according to the adolescent’s educational choice (i.e., whether they attend high school or if they choose an apprenticeship or vocational training). Results have highlighted the importance of neuroticism, conscientiousness, and parental support to predict career decision-making difficulties. Moreover, parental support mediated the relationships between extraversion and agreeableness (fully) and between conscientiousness (partially) and career decision-making difficulties. Finally, the educational choice had no impact on the overall pattern of relationships. Implications for career counselor practices were further discussed.