The interest in the promotion of entrepreneurship is significantly increasing, particularly in those countries, such as Italy, that suffered during the recent great economic recession and subsequently needed to revitalize their economy. Entrepreneurial intention (EI) is a crucial stage in the entrepreneurial process and represents the basis for consequential entrepreneurial actions. Several research projects have sought to understand the antecedents of EI. This study, using a situational approach, has investigated the personal and contextual determinants of EI, exploring gender differences. In particular, the mediational role of general self-efficacy between internal locus of control (LoC), self-regulation, and support from family and friends, on the one hand, and EI, on the other hand, has been investigated. The study involved a sample of 658 Italian participants, of which 319 were male and 339 were female. Data were collected with a self-report on-line questionnaire and analysed with SPSS 23 and Mplus 7 to test a multi-group structural equation model. The results showed that self-efficacy totally mediated the relationship between internal LoC, self-regulation and EI. Moreover, it partially mediated the relationship between support from family and friends and EI. All the relations were significant for both men and women; however, our findings highlighted a stronger relationship between self-efficacy and EI for men, and between support from family and friends and both self-efficacy and EI for women. Findings highlighted the role of contextual characteristics in addition to personal ones in influencing EI and confirmed the key mediational function of self-efficacy. As for gender, results suggested that differences between men and women in relation to the entrepreneur role still exist. Practical implications for trainers and educators are discussed.