Over a decade of research on the relationship between nurse staffing and patient outcomes has demonstrated the important role of nurses in the provision of high-quality, safe care, yet currently, no evidence-based nurse staffing guidelines exist. A systematic review of reviews was conducted to explore reasons why this is the case and recommend directions for future research to improve upon this gap. Authors of the 29 included reviews reported variability in methods and measurement approaches, lack of incorporation of nurse processes and system factors that potentially affect relationships among variables, and overall inconsistencies in results across primary studies. We propose use of an Integrated Framework for a Systems Approach to Nurse Staffing Research to inform the development of applicable conceptual models. Future studies that use a systems approach and focus on establishing causal relationships among variables will potentially strengthen the evidence and advance the science in this area.