Many youth in out-of-home care (OOHC) have experienced victimization in their lifetime making them vulnerable to mental health problems and further victimization. However, little is known about mechanisms behind this continuing victimization, e.g. in the form of bullying victimization, and about possible mediating and moderating factors. This study examined the association between lifetime poly-victimization and later bullying victimization, as well as mediation by internalizing problems, and moderation by OOHC. In total n = 226 youth (n = 117 OOHC, n = 109 biological families) participated, with one of their social/biological caregivers when possible, resulting in subsamples of n = 159 participants (11–21 years) for self-report, and n = 210 participants (8–21 years) for caregiver report. An online survey assessed self-report of bullying victimization in the past six months, as well as self-report and caregiver report of lifetime poly-victimization and internalizing problems. Based on both self-report and caregiver report, youth in OOHC showed higher levels of poly-victimization and internalizing problems than youth in biological families. In self-report, a conditional direct effect of lifetime poly-victimization on bullying victimization was found for youth in OOHC, c′ = 0.18, SE = 0.07, p = .007, while the association was mediated by internalizing problems for youth in biological families, ab = 0.13, 95 % CI 0.020; 10.805. In the caregiver report, there was neither a direct nor a mediated effect of lifetime poly-victimization on bullying victimization. The results stress the importance of considering the high impact of poly-victimization in predicting bullying victimization, particularly for youth in OOHC. For youth in biological families, a mediating effect of internalizing problems was found.