Global health crises require coordination and collaboration among actors and global health agendas including health security, health promotion, and universal health coverage. This study investigated whether national public health institutes (NPHIs) unify agendas and actors, how this can be achieved, and what factors contribute to success. We conducted semi-structured interviews with 24 public health leaders from 18 countries in six WHO regions between 2019 and 2020. Respondents described how NPHIs bridge agendas reporting five strategies that institutes employ: serving as a trusted scientific advisor; convening actors across and within sectors; prioritizing transdisciplinary approaches; integrating public health infrastructures, and training that builds public health capacity. Findings also revealed five enabling factors critical to success: a strong legal foundation; scientific independence; public trust and legitimacy; networks and partnerships at global, national, and local levels; and stable funding. The Covid-19 pandemic underscores the urgency of securing scientific independence and promoting national institutes' responsiveness to public health challenges.