Background: Occupational stress among nurses is commonly linked to staffing shortages and excessive workloads. However, emerging evidence suggests that workplace relationships, particularly with supervisors, physicians, patients, and families, may exert an equally significant, if not greater, influence on nurses’ well-being. Aim: This study investigated whether supervisory and interpersonal stressors outweigh workload-related factors as drivers of occupational stress among nurses in tertiary hospitals and identified demographic factors associated with stress within the Demand–Control–Support framework. Methods: A descriptive cross-sectional survey was conducted among registered nurses in two tertiary hospitals in Delta State, Nigeria. From a population of 714 nurses, 259 with at least two years of clinical experience were selected using a stratified sampling technique. Occupational stress was assessed using the 50-item Expanded Nursing Stress Scale (ENSS), comprising eight stress domains rated on a four-point Likert scale. Domain rankings were based on mean scores, while differences across demographic groups were examined using Mann–Whitney U and Kruskal–Wallis tests at a significance level of p < .05. Results: Nearly two-thirds (65.4%) of participants reported moderate-to-severe stress. Problems with supervisors (M = 3.30) emerged as the highest stressor, followed by patient and family interactions (M = 3.20), both exceeding workload-related stress (M = 3.17). Age significantly influenced stress levels (H = 16.684, p = .001), with nurses aged 21–30 years reporting the highest stress. Years of experience also showed a significant effect (H = 8.002, p = .020), with less experienced nurses reporting greater stress. Gender and marital status were not significant predictors. Conclusion: Supervisory and interpersonal stressors surpassed workload as the primary sources of occupational stress. Findings support the Demand–Control–Support model and highlight the need for interventions that strengthen supervisory support, improve workplace relationships, and support early-career nurses alongside staffing improvements.