Background <p>Nurses’ readiness for disaster response is influenced by stress, self-efficacy, and family support. Understanding these mediating roles is crucial for enhancing readiness and ensuring effective patient care during disasters. This study examined whether self-efficacy and family support can mediate the relationship between stress and readiness for disaster response among nurses.</p> Methods <p>This cross-sectional study included 476 registered nurses. Data regarding demographics, work-related characteristics, perceived family support, and the Perceived Stress Scale-14, General Self-Efficacy Scale, and Readiness for Disaster Response Scale were collected. Descriptive statistics and Pearson’s correlation were used to analyze the data. The mediating roles of self-efficacy and family support were assessed using the PROCESS macro in SPSS; the indirect effects were evaluated using 10,000 bootstrap samples.</p> Results <p>Nurses’ stress negatively correlated with self-efficacy and family support, whereas self-efficacy positively correlated with family support. Nurses’ readiness for disaster response negatively correlated with stress, and positively correlated with self-efficacy and family support. Self-efficacy significantly mediated the relationship between stress and readiness for disaster response; however, family support did not show any significant indirect effect.</p> Conclusions <p>These findings suggest that self-efficacy may play an important role in the relationship between stress and readiness for disaster response conversely, family support—although beneficial—did not significantly mediate this relationship. Considering the cross-sectional nature of the study, causal relationships cannot be inferred. Potential strategies to foster self-efficacy and readiness may include skill training, scenario-based drills, supportive workplace policies, and family engagement.</p>