The current study examined the variables that contribute to the development of Secondary Traumatic Stress in oncology nurses. Symptoms of Secondary Traumatic Stress have been found to mimic those of Posttraumatic Stress Disorder (PTSD) and consist of three main clusters of symptoms including: (a) Intrusion; (b) Avoidance; and (c) Arousal. Oncology nurses are susceptible to the development of Secondary Traumatic Stress due to their continuous interaction with cancer patients who often have traumatic experiences associated with their illness. Research questions regarding what combination of Personal/Professional, Personal Experience with Cancer, Workplace/Workload, and Support and Preparation variables predict General Secondary Traumatic Stress, Professional Secondary Traumatic Stress, Intrusion, Avoidance, and Arousal were explored. The current sample included 66 oncology nurses from three midwestern chapters of the Oncology Nursing Society (ONS). Respondents completed a self-report survey that consisted of a sociodemographic questionnaire, the Professional Quality of Life Scale (ProQOL, Version 5), the Secondary Traumatic Stress Scale (STSS), and a Support and Preparation survey. Sequential multiple regression was used to analyze the five models. Results were fairly consistent across all measures of Secondary Traumatic Stress. Personal/Professional and Personal Experience with Cancer did not explain a statistically significant amount of variance in Secondary Traumatic Stress. However, Workplace/Workload variables did explain a significant amount of variance (8-14%). Specifically, number of deaths was negatively associated with General Secondary Traumatic Stress, Intrusion, Avoidance, and Arousal. Support and Preparation variables were found to be the most significant predictors (explaining approximately 15-22% of the variance) of Secondary Traumatic Stress. Specifically, Support Desired was positively associated with Secondary Traumatic Stress and Support Satisfaction was negatively associated with Secondary Traumatic Stress. These latter two groups of variables represent the most changeable variables in the model, and as such they can be targeted for change to help improve the experiences of oncology nurses, thereby reducing their risk of developing Secondary Traumatic Stress. Due to the dearth of literature currently available on Secondary Traumatic Stress in oncology nurses, it is hoped that this study will help to fill this void in the literature.