Significant progress has been made in recent years in how to optimize processing conditions for bulk glass formation, net-shape forming and the microscopic mechanism of failure. However, the details of the correlation between atomic structure, defects and thermo-mechanical treatments for structure modification and their impact on shear banding for achieving macroscopic ductility are still not well-understood. The present work attempts to shed light on structural (re)ordering, recovery and rejuvenation mechanisms, as well as nanocrystallization in metallic glasses when they are subjected to different casting conditions, relaxation or thermoplastic net-shaping. The findings will be discussed with respect to short- and medium-range order modulation, defect generation and annihilation, and precipitation of secondary phases. The structural changes will be correlated with plastic deformability and failure mechanisms, and the effectiveness of composition tuning and thermo-mechanical processing for plasticity improvement will be analyzed to derive guidelines for property optimization of metallic glasses.