Using holistic-interactionistic theory, the simultaneous nature of risk and protection factors for both males and females (age 6-11 in Wave 1) is examined using Latent Profile Analysis (LPA). Risk/protection classes are estimated using multiple risk factor variables (e.g., physical child abuse) and multiple protective factors (e.g., extracurricular activities). These risk/protection classes were used to predict low academic performance. For both males and females, high risk, low protection individuals were significantly more likely to experience low academic performance than low risk, high protection cases. Gender differences emerged in a class for females that included the importance of parental/peer disapproval of anti-social behavior as a protective factor that was not present for males. Findings support elements of the holistic-interactionistic theory for human development and suggest the need to examine risk and protective factors in combination to account for their shared influences on developmental outcomes. Implications for youths underperforming academically are discussed.