The Nankai Trough in Southwest Japan exhibits a wide spectrum of fault slip, with long-term and short-term slowslip events, slow and fast earthquakes, all associated with different segments down the plate interface. Frictional and viscous properties vary depending on rock type, temperature, and pressure. However, what controls the downdip segmentation of the Nankai subduction zone megathrust and how the different domains of the subduction zone interact during the seismic cycle remains unclear. Here, we model a representative cross-section of the Nankai subduction zone offshore Shikoku Island where the frictional behavior is dictated by the structure and composition of the overriding plate. The intersections of the megathrust with the accretionary prism, arc crust, metamorphic belt, and upper mantle down to the asthenosphere constitute important domain boundaries that shape the characteristics of the seismic cycle. The mechanical interactions between neighboring fault segments and the impact from the long-term viscoelastic flow strongly modulate the recurrence pattern of earthquakes and slow-slip events. Afterslip penetrates down-dip and up-dip into slow-slip regions, leading to accelerated slow-slip cycles at depth and longlasting creep waves in the accretionary prism. The trench-ward migrating locking boundary near the bottom of the seismogenic zone progressively increases the size of long-term slow-slip events during the interseismic period. Fault dynamics is complex and potentially tsunami-genic in the accretionary region due to low friction, off-fault deformation, and coupling with the seismogenic zone.