Background <p>Healthcare workers’ professional attitudes are critical for effective outbreak response. Understanding the drivers of these attitudes is essential for strengthening epidemic resilience, particularly for high-threat pathogens like the Marburg virus.</p> Objective <p>To identify the determinants of healthcare workers’ attitudes toward the Marburg virus disease outbreak response in Northwest Ethiopia.</p> Methods <p>A facility-based cross-sectional study design was conducted from November 30 to December 30, 2025, across three public hospitals in the Awi Zone. Data were collected using a pretested, self-administered questionnaire. Attitudes were measured with an 18-item Likert scale; scores above the mean (&gt;65.6) indicated positive attitudes. Binary logistic regression was used to identify determinants, with statistical significance set at <i>p</i> &lt; 0.05.</p> Results <p>Among 413 healthcare workers (response rate 97.6%), 55.2% exhibited positive attitudes toward Marburg virus disease. Determinants of positive attitudes included male gender (AOR = 2.15, 95% CI: 1.34, 3.45), master of science and above education (AOR = 2.73, 95% CI: 1.48, 5.06), access to disease information (AOR = 1.67, 95% CI: 1.07, 2.62), and good knowledge of Marburg virus disease (AOR = 2.04, 95% CI: 1.36, 3.28).</p> Conclusion <p>While 55.2% of healthcare workers demonstrated positive attitudes, a substantial minority (44.8%) held negative attitudes. Significant determinants included male gender, higher education, access to disease information, and good knowledge. Tailored interventions improving knowledge, ensuring equitable information access, and promoting higher education are recommended.</p>