In an attempt to understand how cumulative risk influences behavioral problems in early adolescence, this study focuses on the mediating and the moderating roles of dysregulation in multiple biological stress systems. In a sample of 223 seventh- and eighth-grade children, cumulative risk included psychosocial factors (family turmoil, parent-child separation, exposure to violence) and physical factors (noise, crowding, housing quality) and sociodemographic characteristics of the adolescents? families (maternal high school drop out, single parent, and poverty). Physiological markers of biological stress dysregulation were cortisol, epinephrine, norepinephrine, fat deposition, resting systolic and diastolic blood pressure, and systolic and diastolic reactivity and recovery. There were adverse effects of cumulative risk on both internalizing and externalizing behaviors. Cumulative risk and biological stress dysregulation had a curvilinear relationship. We found that biological stress dysregulation may have an indirect effect on the relation between cumulative risk and internalizing behaviors. Further, older children were more likely to develop internalizing behaviors when they were exposed to cumulative risk. Biological stress dysregulation moderated the effects of cumulative risk on externalizing behaviors; the inefficient stress regulation in multiple biological systems made children more vulnerable to externalizing behavioral problems when they were living in cumulative risk environment. The importance of understanding both mediating and moderating roles of biological stress dysregulation for behavioral problems was discussed.