Abstract Objective The annual American College of Medical Informatics (ACMI) symposium focused discussion on the national public health information systems (PHIS) infrastructure to support public health goals. The objective of this article is to present the strengths, weaknesses, threats, and opportunities (SWOT) identified by public health and informatics leaders in attendance. Materials and Methods The Symposium provided a venue for experts in biomedical informatics and public health to brainstorm, identify, and discuss top PHIS challenges. Two conceptual frameworks, SWOT and the Informatics Stack, guided discussion and were used to organize factors and themes identified through a qualitative approach. Results A total of 57 unique factors related to the current PHIS were identified, including 9 strengths, 22 weaknesses, 14 opportunities, and 14 threats, which were consolidated into 22 themes according to the Stack. Most themes (68%) clustered at the top of the Stack. Three overarching opportunities were especially prominent: (1) addressing the needs for sustainable funding, (2) leveraging existing infrastructure and processes for information exchange and system development that meets public health goals, and (3) preparing the public health workforce to benefit from available resources. Discussion The PHIS is unarguably overdue for a strategically designed, technology-enabled, information infrastructure for delivering day-to-day essential public health services and to respond effectively to public health emergencies. Conclusion Most of the themes identified concerned context, people, and processes rather than technical elements. We recommend that public health leadership consider the possible actions and leverage informatics expertise as we collectively prepare for the future.