Introduction <p>The birth of an infant with congenital anomalies is a significant stressor for mothers, often leading to emotional challenges such as anxiety, depression, and grief.</p> Objective <p>This study aims to investigate the relationship between psychological resilience, coping strategies, and perceived social support in mothers of infants with congenital anomalies hospitalized in the neonatal intensive care unit (NICU).</p> Methods <p>This descriptive, cross-sectional study involved 345 mothers of infants with congenital anomalies admitted to NICUs at four hospitals. Data were collected using a demographic questionnaire, the Connor-Davidson Resilience Scale (CD-RISC 10), the Multidimensional Scale of Perceived Social Support (MSPSS), and Lazarus and Folkman’s Ways of Coping questionnaire. Statistical analyses were conducted using Pearson correlation, t-tests, and one-way ANOVA with R software, considering a 5% significance level.</p> Results <p>The mean resilience score was 23.52 ± 6.30, with 49% showing low resilience, 35.1% moderate, and 15.9% high resilience. Resilience significantly correlated with coping strategies (<i>p</i> &lt; 0.0001) and perceived social support (<i>p</i> &lt; 0.0001). Positive reappraisal was the most common coping strategy. A moderate relationship between resilience and social support from friends (<i>r</i> = 0.486) and family (<i>r</i> = 0.473) was observed.</p> Conclusion <p>Mothers of infants with congenital anomalies in this study generally reported lower levels of resilience. Higher resilience scores were associated with the use of positive coping strategies and the presence of strong social support. Approaches that emphasize family involvement and provide targeted training in coping skills may be linked to reduced stress and potentially support more effective caregiving experiences in the NICU context.</p> Clinical trial registration <p>Not Applicable.</p>