Background and Purpose: Evidence-based practice (EBP) is essential for improving patient outcomes and healthcare quality. However, its implementation in acute care remains inconsistent due to organisational hierarchies, professional silos, and limited access to continuous professional development (CPD). Nurses play a key role in translating research into practice but often encounter barriers that limit their ability to lead EBP initiatives. Interprofessional collaboration and CPD are recognised enablers of EBP, yet their impact in acute care requires further investigation. This study explores how interprofessional collaboration, nurse-led initiatives, and CPD influence EBP adoption. Methods and Procedures: A collective qualitative case study was conducted across two acute care hospitals in the East Midlands, England. Data collection included 25 semi-structured interviews, nonparticipant observations, and document analysis over six years, with an intensive fieldwork phase in 2022. Thematic analysis was used to identify key patterns related to EBP adoption, interprofessional collaboration, and nurse-led knowledge implementation. Results: Nurses actively advocated for EBP integration but often worked independently due to the absence of formal collaboration structures. Interprofessional collaboration facilitated knowledge-sharing and decision-making, yet hierarchical constraints limited nurses’ influence in clinical governance. CPD enhanced nurses’ confidence and ability to challenge outdated practices, but disparities in access led to inconsistent EBP engagement across nursing teams. Conclusion: Structured CPD, interdisciplinary collaboration, and inclusive decision-making are essential for EBP adoption. Addressing hierarchical constraints and resource limitations is crucial for sustaining evidence-driven care. Future research should explore the long-term sustainability of EBP implementation.