Background: Nursing education enhances knowledge and skills, fostering the development of nurses into highly competent professionals. Clinical Instructors (CIs) play a crucial role in bridging university education and real-world clinical experiences and are responsible for facilitating learning in clinical practice. Aim: To explore the perceived barriers and facilitators encountered by CIs in supervising nursing students during clinical placements. Method: An exploratory-descriptive qualitative design was adopted. Data were collected through two focus groups with CIs at the Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) National Cancer Institute Foundation of Milan, and analyzed using reflexive thematic analysis. Results: Twelve CIs participated. The analysis generated six themes; three themes (Mentorship, Relationships and Learning Processes, and Improvement of Learning Processes) represented facilitators and three (From Boomers to Zoomers, Aspects of Crisis within the Profession, and Managing Student Learning) represented barriers. The categorization into barriers and facilitators was applied after theme generation to facilitate interpretation. Conclusion: Findings indicate that facilitators promote a supportive learning environment, while barriers hinder the effectiveness of clinical education. Strengthening academic-clinical collaboration, expanding CI training, and enhancing mentorship programs may help improve clinical supervision. Future research should explore collaboratively developed tools and feedback processes between academic and clinical settings to better support CIs.