Recent studies indicate that the transition from school to work is a critical juncture in shaping the professional future of youth at risk. This period may thus serve as a window of opportunities for fostering employability among these youths and, thereby, for promoting their social mobility. However, systematic evaluations of intervention programs aimed at fostering employability among at-risk adolescents—and especially in a multi-cultural context—are relatively few. The current study describes the strengths and weaknesses of a pilot, nation-wide, multi-cultural, holistic intervention program, aimed at fostering employability among at-risk adolescents before they actually enter the labor market. The program integrated efforts in three main domains: cultivating work-related skills, fostering personal and interpersonal skills, and providing a supportive personal and group climate. During the years 2011–2013, the program was operated in 40 localities in Israel and in three culturally different sectors: The Jewish-Israeli majority sector in the periphery, the Ultra-Orthodox Jewish minority sector, and the Israeli-Arab (Muslim) minority sector. The current study describes the results of an evaluation study that accompanied the implementation of the program in nine representative localities (117 adolescents, ages 14–19) during 2012.Overall, the functioning of the adolescents (as evaluated by the professional program instructors) improved in all examined work-related domains: personal-emotional functioning, work-related functioning, CV writing ability, and future education prospects. Regression analyses highlighted several factors as predictive of improvement in the different employability-related domains, most notably, having a working father, being active in group meetings, having no Internet connection at home, helping other participants in the program, and being involved in selecting the topics of a professional course. Importantly, this improvement was linked with the cultural affiliation of the participants, and participants from the different sectors indicated different factors as contributing to their advancement.The results of this evaluation study suggest that intervention programs for promoting employability among at-risk adolescents should integrate a holistic and flexible national model with adaptations by local steering committees, whose members are from the same cultural group as the participating adolescents. Such a strategy will enable each unique community to tailor the local operation of the program to the culturespecific needs of—and to maximally utilize the resources available for—the different sectors in a multi-cultural society, while establishing a dialogue and reciprocal learning in national forums. A dilemma has been identified, however, with respect to increasing the local involvement of the national committee to provide the local committees with different viewpoints.