The ability of high-temperature superconductors (HTSs) to carry very large currents with almost no dissipation makes them irreplaceable for high-power applications. The development and further improvement of HTS-based cables requires an in-depth understanding of the superconducting vortex dynamics in presence of complex pinning landscapes. We present a critical current analysis of a real HTS sample in a magnetic field by combining state-of-the-art large-scale Ginzburg-Landau simulations with reconstructive three-dimensional scanning transmission electron microscopy tomography of the pinning landscape in Dy-doped YBa$_2$Cu$_3$O$_{7-\delta}$. This methodology provides a unique look at the vortex dynamics in the presence of a complex pinning landscape, responsible for the high current-carrying capacity characteristic of commercial HTS wires. Our method demonstrates very good functional and quantitative agreement of the critical current between simulation and experiment, providing a new predictive tool for HTS wires design.