This study examined the coronavirus disease 2019 (COVID-19) preparedness and response of the health system (HS) in Hanoi, Vietnam, and identified enabling factors and barriers. This cross-sectional, mixed-methods study was conducted in 4 urban and peri-urban districts that included some wards with COVID-19-positive cases and some without. The US Centers for Disease Control and Prevention (CDC) analytical frameworks were used. Overall, 10% of health facilities (HFs) failed to fully implement COVID-19 risk determination; 8.8% failed to fully implement stronger community partnerships with local stakeholders to support public health (PH) preparedness; 35% and 2.5% incompletely implemented and did not implement evaluation of PH emergency operations, respectively; 10% did not identify communication channels to issue public information, alerts, warnings, and notifications; 25% incompletely implemented identification, development of guidance, and standards for information; 72.5% had good preventive and treatment collaboration; and 10% did not fully implement procedures for laboratory testing and reporting results. Enablers included sufficient infrastructure and equipment, strong leadership, and good cross-public-sector collaboration with police and military forces. Barriers included workforce constraints, overburdened and inconsistent reporting systems, inappropriate financial mechanisms, ambiguous health governance, and lack of private-sector engagement. Nonetheless, the HS preparedness and response were satisfactory, although further coordinated efforts in evaluation, coordination, communication, and volunteering remain necessary.