There is increasing recognition of the value added by integrating traditionally separate efforts to protect and promote worker safety and health. This paper presents an innovative conceptual model to guide research on determinants of worker safety and health and to inform the design, implementation and evaluation of integrated approaches to promoting and protecting worker health. This model is rooted in multiple theories and the premise that the conditions of work are important determinants of individual safety and health outcomes and behaviors, and outcomes important to enterprises such as absence and turnover. Integrated policies, programs and practices simultaneously address multiple conditions of work, including the physical work environment and the organization of work (e.g., psychosocial factors, job tasks and demands). Findings from two recent studies conducted in Boston and Minnesota (2009-2015) illustrate the application of this model to guide social epidemiological research. This paper focuses particular attention on the relationships of the conditions of work to worker health-related behaviors, musculoskeletal symptoms, and occupational injury; and to the design of integrated interventions in response to specific settings and conditions of work of small and medium size manufacturing businesses, based on a systematic assessment of priorities, needs, and resources within an organization. This model provides an organizing framework for both research and practice by specifying the causal pathways through which work may influence health outcomes, and for designing and testing interventions to improve worker safety and health that are meaningful for workers and employers, and responsive to that setting's conditions of work.