In this 49-minute Presidential Lecture, explore how extreme-scale computation bridges particle physics to nuclear physics through systematic calculations. Discover the first examples of first-principles computations of nuclear reactions and learn about new theoretical and experimental work revealing the pressure distribution inside protons. Examine the growing role of systematically-exact, physics-informed machine learning approaches in understanding matter's structure from the quark level to nuclei. Presented by Phiala Shanahan at the Simons Foundation on April 23, 2025.