Background <p>Many people encounter traumatic events throughout their lives. Thus, trauma-informed care is necessary within the healthcare system. However, limited research has addressed how adequately nurses are prepared to apply trauma-informed care and the factors affecting its implementation in various clinical settings. This study examined nurses’ knowledge, attitudes, and practices (KAP) regarding trauma-informed care, as well as its enablers and barriers.</p> Methods <p>A cross-sectional study was conducted between July and November 2024, using a stratified random sample of 291 nurses from two large tertiary hospitals in Saudi Arabia. Data were collected using the KAP of the Trauma-Informed Practice Scale and Barriers and Enablers to Trauma-Informed Care Implementation measures.</p> Results <p>Only 56.4% of the sample had received education related to trauma-informed care. Overall, the nurses’ KAP regarding trauma-informed care was moderate. Perceived barriers primarily included external structural factors, whereas enablers were mainly found within internal services and staff roles. Regression analyses showed that the perception of enablers and barriers explained 44.4% of the variance in nurses’ knowledge (F (2, 290) = 115.02, p &lt; 0.001), 55.8% of the variance in attitude (F (2, 290) = 181.71, p &lt; 0.001), and 54.3% of the variance in practice (F (2, 290) = 171.19, p &lt; 0.001).</p> Conclusions <p>The results show a need to enhance trauma-informed care knowledge among nurses. Multilevel intervention, including organizational support and structural resources, is also needed to facilitate the effective implementation of trauma-informed care.</p> Clinical trial number <p>Not applicable.</p>