The multiexpedition Integrated Ocean Drilling Program/International Ocean Discovery Program (IODP) Nankai Trough Seismogenic Zone Experiment (NanTroSEIZE) project was designed to investigate fault mechanics and seismogenesis along subduction megathrusts through direct sampling, in situ measurements, and long-term monitoring in conjunction with allied laboratory and numerical modeling studies. Overall NanTroSEIZE scientific objectives include characterizing the nature of fault slip and strain accumulation, fault and wall rock composition, fault architecture, and state variables throughout the active plate boundary system. Expedition 380 was the twelfth NanTroSEIZE expedition since 2007. Expedition 380 focused on one primary objective: riserless deployment of a long-term borehole monitoring system (LTBMS) in Hole C0006G in the overriding plate at the toe of the Nankai accretionary prism. The LTBMS installed in Hole C0006G incorporates multilevel pore-pressure sensing and a volumetric strainmeter, tiltmeter, geophone, broadband seismometer, accelerometer, and thermistor string. Similar previous LTBMS installations were completed farther upslope at IODP Sites C0002 and C0010. The ~35 km trench–normal transect of three LTBMS installations will provide monitoring within and above regions of contrasting behavior in the megasplay fault and the plate boundary as a whole, including a site above the updip edge of the locked zone (Site C0002), a shallow site in the megasplay fault zone and its footwall (Site C0010), and a site at the tip of the accretionary prism (the Expedition 380 installation at Site C0006). In combination, this suite of observatories has the potential to capture stress and deformation spanning a wide range of timescales (e.g., seismic and microseismic activity, slow slip, and interseismic strain accumulation) across the transect from near-trench to the seismogenic zone. Expedition 380 achieved its primary scientific and operational goal with successful installation of the LTBMS to a total depth of 457 m below seafloor in Hole C0006G. The installation was conducted in considerably less time than budgeted, partly because the Kuroshio Current had shifted away from the NanTroSEIZE area after 10 y of seriously affecting D/V Chikyu NanTroSEIZE operations. After Expedition 380, the LTBMS was successfully connected to the Dense Oceanfloor Network System for Earthquakes and Tsunamis (DONET) in March 2018 using the remotely operated vehicle Hyper-Dolphin from the Japan Agency for Marine-Earth Science and Technology (JAMSTEC) R/V Shinsei Maru.