Purpose: This study examined the effects of clinical nurses' communication skills, critical reflection, and professional self-efficacy on medication safety competency. Methods: The participants were 150 clinical nurses with at least 12 months of experience in a tertiary hospital. Validated scales for assessed communication skills, critical reflection, professional self-efficacy, and medication safety competency. Data were analyzed using SPSS 29.0 with descriptive statistics, t-tests, ANOVA, correlation, and regression analyses. Results: The mean medication safety competency score was 4.24 ± 0.49, with the highest subscale scores observed in crisis management, patient-centered medication management, and problem-solving. Nurses aged 36 years and older and with over 6 years of experience demonstrated significantly higher medication safety competency. Medication safety competency showed positive correlations with communication skills (r = .68, p <. 001), critical reflection (r = .70, p < .001), and professional self-efficacy (r = .61, p <. 001). Regression analysis revealed these factors as significant predictors, collectively accounting for 57.5% of the variance. Conclusion: Communication skills, critical reflection, and self-efficacy significant determinants of nurses’ medication safety competency. Educational programs targeting theses domains are essential to improve medication safety. Further research is needed to assess and refine such interventions, thereby supporting continuous professional development and improved patient outcomes.