Background: Patient safety is a fundamental component of healthcare quality and a critical responsibility of nursing staff. Various organizational, individual, and environmental factors may influence patient safety outcomes in clinical settings. Aim: to investigate the factors affecting patients’ safety as perceived by nurses. Research Design: a descriptive research design was used to achieve the aim of this study. Setting: The study was conducted at King Khalid Hospital in Najran region, affiliated to the Ministry of Health at Saudi Arabia. Sample: A convenient sample of (130) nurses having at least one year of experience, include male & female and at work during the period of data collection were composed the study sample. Tools: Two tools were used for the study as follow; I) personal characteristics and workrelated data sheet and II) Nurses’ perception of factors affecting patient safety questionnaire. Results: The study revealed that the highest percentage of participants were females (71.5%) aged 30 to less than 40 years (52.3%), with Saudi nationality comprising 76.9% of the sample, nearly half held a bachelor’s degree (44.6%) and 93.1% had not received prior patient safety training. The current study demonstrated that teamwork factor showed the highest factor loading, identifying it as the single most influential domain driving nurses' overall perception regards factors affecting patient safety. There was a significant negative correlations between teamwork and individual performance factors, as well as between work-environment factors and both individual performance and patient safety factors. Organizational factors also correlated negatively with patient safety. Conversely, significant positive correlations emerged between organizational factors and both work-environment and staffing factors. Finally, a statistically significant gender-based difference was observed regarding teamwork perceptions, with male nurses scoring a higher mean than female nurses. Conclusion: The present study highlights that patient safety is a multifaceted concept influenced by a complex interaction of personal, organizational, environmental, and staffing-related factors. While nurses possess clinical experience, the lack of continuous education in patient safety limits the translation of experience into safe practice. Recommendation: The healthcare institutions should implement mandatory, ongoing patient safety training programs to bridge existing knowledge gaps and boost clinical competence. Simultaneously, organizations should establish robust wellness and psychological support systems to actively mitigate nurse burnout and alleviate job stress. Furthermore, fostering a non-punitive "Just Culture" is essential.