Suicide, the second leading cause of death among adolescents, requires an integrative approach to maximize the effectiveness of prevention efforts. The current study draws on the social-ecological model and its relevance to the ecosystem at Vocational Education and Training (VET) high schools in the context of suicide prevention. The study examined the school-related factors of school connectedness, academic self-efficacy and school autonomy support in relation to suicidal thoughts and behavior. Participants included 5688 students (mean age 15.58) drawn from 62 vocational high schools across Israel. Structural equation modeling revealed that school connectedness and academic self-efficacy exhibit negative links to suicide ideation and behavior; moreover, these links were partly mediated by depressive symptoms. School autonomy support was found to be positively linked to suicide ideation and suicide attempts. The paper discusses the results with respect to suicide prevention efforts in the unique context of adolescents attending vocational schools.