Medium-range ordering (MRO) and structural heterogeneity in Zr-Cu-Co-Al metallic glasses (MGs) are characterized and their influence on ductility is investigated. Angular correlation analysis and digital reconstruction of dark-field images of nanodiffraction patterns acquired using four-dimensional scanning transmission electron microscopy reveal structural symmetries of the MRO regions localized at the nanometer scale, as well as their size distribution. The type and size distribution of the MRO regions change as a function of MG composition, with some MRO types clearly resembling the symmetry of known intermetallic phases. The MRO appears to become more structurally frustrated (e.g., lack of sixfold symmetry) when compositional heterogeneity increases, which may be inherently connected to the observed increase in ductility. Based on this hypothesis, mesoscale deformation simulations incorporating the experimentally acquired MRO information (types and sizes) are performed to gain insights on potential MRO-ductility relationship. Different types of MRO are assumed to have different properties and their influences on the stress-strain curve, the largest connected-free-volume, and the total number of extreme strain value sites are investigated parametrically. The simulation results reveal that the degree of heterogeneity in the MRO structures, in terms of both type and size, correlates directly with the ductility of the MGs.