As one of the important factors to predict future sustainable development, the difficulty of career decision-making has aroused widespread concern in psychological research. Core self-evaluation and career calling have a positive impact on college students’ career development, employees’ organizational behavior, life satisfaction, and life meaning, thus promoting individual sustainable development. Based on the Social Cognitive Career Theory (SCCT), this study mainly discusses the positive role of core self-evaluation and career calling in overcoming college students’ career decision-making difficulties, which provides support for strengthening theory and proposing educational countermeasures. This study investigates the relationship among core self-evaluation, career calling, and career decision-making difficulties for 483 Chinese college students. The results show that core self-evaluation positively predicts career calling, while core self-evaluation and career calling negatively predict career decision-making difficulties. Accordingly, career calling plays a partial mediating role between core self-evaluation and career decision-making difficulties. Therefore, college students’ career calling can be enhanced by improving their core self-evaluation, so as to further solve the difficulties in career decision-making. In the future, effective strategies should be taken to reduce the career decision-making difficulty for students’ sustainable development.