We propose an integrated model of learning demands, work-related resources, and job stressors that incorporates core assumptions of work design in predicting processes of learning and performance as well as health impairment. The model was tested in a heterogeneous sample of 830 employees using structural equation modeling. Empirical results largely support theoretical assumptions. Learning demands and work-related resources were positively related to intrinsic motivation and creative performance. Job stressors and low work-related resources were predictive for health impairment. The suggested tripartite taxonomy reconciles inconsistent research findings on the impact of work characteristics. The model provides practical guidance for work analysis and design by clarifying relationships between established work characteristics, job performance, and worker health.