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Despite decades of increased research and funding, youth mentoring programs, overall, yield small effects on youth outcomes. As a result, there are growing calls for programs to utilize the mentoring relationship as context for intentional, targeted skills development, in which mentors employ targeted skills designed to match the presenting concerns of mentees. This targeted approach contrasts with the historically dominant, non-specific friendship model, which holds that a supportive relational bond-alone-promotes positive developmental change. The current study is a follow-up meta-analysis using a comprehensive dataset of all intergenerational, one-on-one mentoring program evaluations published between 1975 and 2018, investigating the comparative impact of targeted, skills-based versus non-specific, relational approaches to mentoring. Analyses of 48 mentoring studies of youth outcomes (average youth age of 12.25 years old) revealed the overall effect size of targeted programs to be more than double that of non-specific relational approaches, with significant moderator effects on academic, psychological, and social functioning. Findings suggest that youth mentoring programs can promote positive outcomes, particularly when mentors employ targeted approaches matched to the needs of their mentees.