DIII-D research is addressing critical challenges in preparation for ITER and the next generation of fusion devices through focusing on plasma physics fundamentals that underpin key fusion goals, understanding the interaction of disparate core and boundary plasma physics, and developing integrated scenarios for achieving high performance fusion regimes. Fundamental investigations into fusion energy science find that anomalous dissipation of runaway electrons (RE) that arise following a disruption is likely due to interactions with RE-driven kinetic instabilities, some of which have been directly observed, opening a new avenue for RE energy dissipation using naturally excited waves. Dimensionless parameter scaling of intrinsic rotation and gyrokinetic simulations give a predicted ITER rotation profile with significant turbulence stabilization. Coherence imaging spectroscopy confirms near sonic flow throughout the divertor towards the target, which may account for the convection-dominated parallel heat flux. Core-boundary integration studies show that the small angle slot divertor achieves detachment at lower density and extends plasma cooling across the divertor target plate, which is essential for controlling heat flux and erosion. The Super H-mode regime has been extended to high plasma current (2.0 MA) and density to achieve very high pedestal pressures (~30 kPa) and stored energy (3.2 MJ) with H98y2 ≈ 1.6–2.4. In scenario work, the ITER baseline Q = 10 scenario with zero injected torque is found to have a fusion gain metric independent of current between q95 = 2.8–3.7, and a lower limit of pedestal rotation for RMP ELM suppression has been found. In the wide pedestal QH-mode regime that exhibits improved performance and no ELMs, the start-up counter torque has been eliminated so that the entire discharge uses ≈0 injected torque and the operating space is more ITER-relevant. Finally, the high- (⩽3.8) hybrid scenario has been extended to the high-density levels necessary for radiating divertor operation, achieving ~40% divertor heat flux reduction using either argon or neon with Ptot up to 15 MW.