Structural heterogeneity at the nanoscale such as medium-range order (MRO) in metallic glasses (MGs) has been suggested by theories and simulations for many years and recently been observed by experiments. However, its correlation with plastic deformation is still poorly understood and investigation into this correlation has just begun. In this study, we first propose a correlation between the properties of shear transformation zone (STZ) and the local structural information at the MRO length scale. As revealed by experiments, the MRO exhibits different types of atomic order and symmetry in MGs depending strongly on the processing history and service condition. We then carry out STZ dynamics simulations to document effects of volume fraction and symmetry of dissimilar STZs (derived from experimental characterization of the MRO) on shear banding dynamics and stress-strain behavior. In particular, a “precipitation-hardening” effect is observed and “strain frustration” is introduced to explain and better understand the influence of nanoscale structural heterogeneity on mechanical behavior of MGs. Our approach intends to provide new fundamental insights into the relationship between the mechanical properties of MGs and their MRO-level structural heterogeneities.