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Background: Stress has become more common among healthcare workers in recent years, which greatly impacts nurses. In Pakistan, specifically in Karachi, these challenges are intensified by high patient inflow and resource constraints. Such stress can negatively impact nurses' mental and physical well-being, job satisfaction, and quality of patient care. Understanding these stressors is crucial for developing strategies to improve working conditions and healthcare outcomes. Aim: To assess workload-related stress levels and determine its prevalence among nurses. Methodology In this cross-sectional study, 150 nurses with valid PNC cards at a tertiary care hospital in Karachi were selected through convenient sampling. Data was collected through questionnaires. The survey included queries related to demographic variables and factors contributing to work-related stress. The data was then analyzed, with results presented in terms of percentages, frequencies for qualitative variables, and mean values with standard deviations for quantitative variables. The Chi-square test was used to explore the relationship between demographic factors and nurses' attitudes towards workload-related stress. Results The results showed that 50.0 % of the participants were found in highly stressed due to workload & 69.3 % were found exhausted at the end of duty hours. Conclusion The research emphasizes the significance of stress management in critical care settings, where a significant number of participants’ work. These findings underscore the urgent need for effective interventions and strong support systems to lessen the stress burden and its wide-ranging impact within the healthcare sector, ultimately improving the well-being of healthcare professionals. This study spotlights the alarming frequency of work-related stress in healthcare professionals and its associated consequences. It has specifically identified noticeable shifts in behaviour and clear signs of depression among the participants.