Individuals with problem solving deficits, and higher levels of neuroticism and hopelessness, are at increased risk for suicide, yet little is known about the interrelationships between these vulnerability characteristics. In a sample of 223 low-income, primary care patients, we examined the potential mediating role of hopelessness on the relation between neuroticism and suicidal behavior, and the potential moderating role of social problem solving ability. Participants completed self-report questionnaires: Suicidal Behaviors Questionnaire-Revised, Social Problem Solving Inventory-Revised, Beck Hopelessness Scale, and NEO Five Factor Inventory. Models were tested using bootstrapped moderated mediation techniques. There was a significant indirect effect of neuroticism on suicidal behavior through hopelessness, and this indirect effect was moderated by social problem solving ability. Patients with greater neuroticism also manifest greater levels of hopelessness and, in turn, more suicidal behavior, and these relations are strengthened at lower levels of social problem solving. Interventions that increase social problem solving ability and reduce hopelessness may reduce suicide risk.