Nursing homes (NHs) are crucial for de-hospitalization and addressing the needs of non-self-sufficient individuals with complex health issues. This study investigates the patient safety culture (PSC) in NHs within a northern Italian region, focusing on factor influencing overall safety perceptions and their contributions to subjective judgements of safety. A cross-sectional study was conducted on 25 NHs in the Autonomous Province of Trento. The Nursing Home Survey on Patient Safety Culture (NHSPSC) was utilized to assess PSC among NH staff. Multilevel linear regression and post hoc dominance analyses were conducted to investigate variabilities in PSC among staff and NHs and to assess the extent to which PSC dimensions explain overall perceptions of PS. Analysis of 1080 questionnaires (44% response rate) revealed heterogeneity in PSC across dimensions and NHs, with management support, organizational learning, and supervisor expectations significantly influencing overall safety perceptions. Despite some areas of concern, overall safety perceptions were satisfactory. However, the correlation between individual dimensions and overall ratings of safety was moderate, suggesting the need to enhance the maturity level of PSCs. Promoting a shift in PSC could enhance transparency, prioritize resident safety, empower nursing staff, and increase family satisfaction with care provided in NHs. The support provided by management to PSC appears essential to influence NH staff perceptions of PS.