Technical advancements in the operating room setting continue, and the concept of the hybrid operating room is promoted and accepted worldwide. The hybrid setting means inclusion of radiology in the already complex environment of a traditional operating room. Collaboration in this type of environment becomes essential and investigating how the nursing staff experiences this collaboration in the hybrid operating room is needed. The aim of the study was to investigate how the nursing staff from the specialties of surgery, anesthesiology, and radiology experienced collaborating in a hybrid operating room. Explorative qualitative design was used. Five focus groups consisting of operating room nurses, operating room assistant nurses, nurse anesthetists, assistant nurse anesthetists, and radiographers were included in the study. Interviews using semistructured questions were conducted. Directive content analysis was used for the data analysis. The following categories revealed: (1) different patient safety perspectives; (2) responsibilities being shared and divided; (3) collaboration becoming better over time; (4) uneven division of labor in a strained work situation and different terms of employment; (5) lack of education and joint meetings; and (6) environmental constraints for satisfying collaboration. The nursing staff in the hybrid operating room highlighted they worked toward a common goal but prioritized their own specific tasks rather than the procedure as a whole. This, together with the uneven task distribution and unclear responsibilities, could create tension between the different staff categories, impacting procedures negatively. The results revealed the importance of proper preparation of the staff to work in the hybrid operating room. Having team building activities, common meetings, relevant training to meet educational needs, and adjusting the team composition could improve hybrid operating room collaboration and improve patient safety and outcomes.