Background: Every day doctors, pharmacists, nurse practitioners, and other healthcare professionals (HCPs) look for solutions to a variety of clinical problems. Evidence-based practice (EBP) approach allows HCPs to obtain the best evidence as soon as possible to quickly resolve these clinical issues and apply that knowledge in clinical practice to improve patient outcomes. Aim: To assess healthcare professionals' EBP knowledge, attitude, and skills towards EBP. Method: A descriptive cross-sectional study was carried out at Specialized Medical Hospital in Dakahlia Governorate, Egypt. The researchers used a rubric observational checklist and a self-administrated questionnaire for data collection and distributed these tools to 120 HCPs including nurses, physicians, and pharmacists in October 2022. Results: Greater than two-thirds (62.5%) of the HCPs displayed a poor EBP knowledge score level with an average of 28.07(5.75) marks. Moreover, 98.3% of them displayed an incompetent skill score level with an average of 57.80(6.31) marks. Concerning their attitude, 66.7% of the HCPs reflected a positive attitude towards EBP with an average of 38.32(3.57). Conclusion: The majority of the HCPs had a poor knowledge score level and incompetent skills score level regarding EBP. Moreover, about two-thirds of them showed a positive attitude toward EBP. Recommendations: Designing and implementing educational programs about EBP in healthcare settings as a technique for ongoing training and education for professional development to improve the competencies needed to apply EBP.