By drawing on the Job Demands and Resources Model, this review article develops a conceptual framework to advance theoretical understanding of the relationship between job-related demands and resources, employee well-being and innovativeness. In conditions characterized by too high levels of demands, employees may suffer from burnout. When job resources are high, they are likely to feel engaged with their work. Burnout in turn can be seen as an inhibitor of innovativeness, and work engagement as an antecedent to innovativeness, mediating the effects of resources and demands at work on innovativeness. We further argue that innovativeness can function as a resource or a demand, depending on how it is managed. In addition to understanding the dual role of innovativeness, the identification of job-specific demands and resources is central to supporting employee well-being and, subsequently, innovativeness. The implications of the proposed conceptual framework for academic researchers and managers are discussed.