Background: Polypharmacy and the use of potentially inappropriate medications are frequent safety issues among nursing home (NH) residents. Deprescribing can significantly reduce the number of drugs used, medication costs, and mortality. This qualitative study sought to understand and compare the perceptions and practices of nurses, pharmacists, and physicians regarding deprescribing in Swiss NHs, referring to an implementation approach on three levels of action: the individual, the institution, and the healthcare system. Methods: Two focus groups were held with 21 participants: one focus group with 11 pharmacists, another with 10 nurses and six semi-structured interviews with physicians were conducted and focused on their individual experience and practices. They were audiotaped and fully transcribed, and a content analysis was performed using to MAXQDA (Ver 12) software. Results: (1) At an individual level, physicians were concerned by consequences of deprescribing in terms of safety. Nurses were closest to residents and stressed the importance of finding the right time, creating a bond of trust before deprescribing and considering the purpose of the stay in the NH. Pharmacists relied on structured guides for deprescribing, which led their reflection and practice. All professionals saw the complexity of the clinical situations, as well as residents’ and relatives’ fears of interruption of care. (2) At an institutional level, the professionals stressed the lack of time to discuss patients’ health and treatment, while pre-existing interprofessional collaboration, specifically, quality circles, seemed useful tools to create common knowledge. In order to reduce prescriptions, better coordination between physicians, nurses, pharmacists and specialists seemed crucial. (3) At the health system level, funding still needs to be provided to consolidate the process, go beyond organisational constraints and ensure deprescribing serves the patient’s wellbeing above all. Conclusions: At the individual level of implementation, the different healthcare professionals expressed specific concerns about deprescribing, depending on their defined role in NHs. Their perspective about the different levers to promote deprescribing at institutional and healthcare system levels converge towards interprofessional collaboration supported by the healthcare system. Specific funding and incentives are therefore needed to support a sustainable interprofessional team.