For 40 years, the Government-University-Industry-Research Roundtable (GUIRR) at the National Academies of Sciences, Engineering, and Medicine has played a crucial role as a convener and advocate for its members and for the broader scientific enterprise. GUIRR celebrated its 40th anniversary at a workshop held June 25-26, 2024, in Washington, DC. The gathering served as an opportunity to both reflect on the roundtable’s achievements and look forward to new directions through an examination of the “triple helix” of investments, innovation, and partnerships in the U.S. science and technology environment. This publication highlights the presentations and discussion of the workshop.