Bone is the third most common site of metastatic spread; bladder, breast, kidney, lung, melanoma, prostate, thyroid, and uterine cancer all commonly metastasize to bone and often bone can be the first site attacked. Microwave ablation (MWA) offers a minimally invasive approach for palliative treatment of bone metastases, as well as primary bone tumors. Compared to other ablative energy modalities, microwaves can radiate through low impedance tissue, such as bone, while providing a fast treatment time. However, there are few published studies describing biophysics of MWA in bone. This study investigates the use of an experimental directional MWA (DMWA) applicator, previously optimized for liver ablation, for treatment of metastatic tumors in vertebral bodies. An experimental 14-gauge DMWA applicator previously characterized in ex vivo and in vivo liver tissues was used in this study. A 3D finite element method solver (COMSOL Multiphysics v5.5) was used to simulate the electromagnetic radiation pattern and subsequent heat transfer of one and two DMWA applicators in an anatomically representative model. Temperature dependent tissue biophysical properties were employed for cortical bone, cancellous bone, cartilage, spinal cord, tumor, and muscle. Ex vivo microwave ablations were performed in lumbar and thoracic vertebrae excised from domestic swine within 3 h post-mortem. The DMWA applicator was inserted through the cortex with its backside adjacent to the dorsal surface of the vertebral body aiming ventrally. Fiber optic temperature sensors were placed on the ventral surface of the spinal canal and in the center of the vertebral body. The vertebrae were cross-sectioned for measurement of the visible ablation zone. Simulations of two DMWA applicators (30 W each, 300 s) in a vertebral body with a 2 cm tumor having biophysical properties mimicking muscle tissue yielded simulated ablation zones 2.5 cm long × 1.5 cm tall × 2.0 cm wide with a near-rectangular shape (as assessed by the 55°C isotherm). Simulations of two DMWA applicators (30 W each, 300 s) in a vertebral body with a 2 cm tumor having biophysical properties mimicking cortical bone yielded simulated ablation zones 2.5 cm long × 1.5 cm tall × 1.5 cm wide in the center and 2.0 cm wide on the sides with a butterfly-type shape. The 45°C isotherm did not extend to the spinal cord domain in either simulation. Ex vivo DMWA experiments are in progress and will be presented at the meeting. DMWA offers the potential for targeted treatment of metastatic and primary tumors in vertebral bodies and other bone sites.