We aimed to explore the predictive value of screening for distress alone, hope alone, or a combination of both. In a multi-center prospective study, 37 English-speaking Adolescents and Young Adults (AYAs) with cancer and 40 parents completed validated instruments at diagnosis (“baseline”) and 3–6 months later (“follow-up”). Correlated regression models described associations. Within each instrument, baseline and follow-up scores were associated. However, only a composite hope/distress score predicted all three patient-centered outcomes. Multi-dimensional screens incorporating positive and negative psychosocial constructs may predict patient-centered outcomes better than isolated, single-construct instruments.