Identifying ways to ensure resident safety is increasingly becoming a priority in residential settings and nursing homes. The aim of this qualitative systematic review was to identify, describe, and assess research evidence on managers' perceptions regarding the barriers and facilitators of daily resident and patient safety work in residential settings and nursing homes. A qualitative systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis checklist. Published studies were sought through academic databases: Academic Search Premier, CINAHL, PubMed (MEDLINE), Scopus, SocINDEX, and Web of Science Core Collection in April 2023. Finally, 12 studies were included. The results of the included studies were synthesized using thematic synthesis after data extraction. According to the results, (1) competent staff and material resources; (2) management and culture; (3) communication, networks, optimal use of expertise; and (4) effective use of guidelines, rules, and regulations play a significant role in the success of resident and patient safety work. The findings revealed that promoting resident safety should not be seen solely as the responsibility of individual residential or nursing home personnel, as it requires multiprofessional cooperation and access to wider networks. Staff and managers must be receptive to learning, changing, and improving safety. Moreover, to ensure resident safety, it is essential to ensure that the organizations support safety work in residential and nursing home units.