The Democratic Republic of Congo (DRC) experiences several disease outbreaks every year. In 2023 alone, the DRC faced outbreaks of Mpox, measles, yellow fever, vaccine-derived polio, malaria, and cholera, alongside humanitarian crises in some regions. Despite the expertise and experience in responding to such epidemics, the timely detection and response to public health emergencies remained a significant challenge, primarily due to challenges in coordination. Following the country´s 10th Ebola viral outbreak from 2018-2020 which led to more than 2,000 deaths, the DRC government committed to establishing a National Public Health Institute (NPHI) to centralize and provide leadership for the public health functions involved in the prevention, detection, and response to disease outbreaks. The NPHI was legally established in April 2022 and began its operations in September 2022 after the appointment of its leadership team. Since then, the country has achieved improved coordination of outbreak response through the establishment of an incident management system and an emergency operations centre, the launch of a coordinated approach to public health research, and enhanced mortality surveillance. Enabling factors for the establishment of the NPHI included political will and strong partnerships with stakeholders. However, challenges during the setup and early phases of its operations, such as resistance to change, delays in mobilising funding, and coordinating support, were also noted. In this paper, we document some of the key lessons learned during the establishment of the NPHI in the DRC, the early successes, how the challenges encountered were addressed, and insights for countries intending to establish their own NPHIs.