This study examined the differential sensitivity of intramedullary spinal cord tumors (IMSCTs) and healthy tissue to focused ultrasound (FUS) and microbubbles in a rat model of IMSCT. F98 glioma cells were injected into spinal cords of F344 rats. FUS (580 kHz, 10 ms bursts, 1 Hz pulse repetition frequency, 40 s) was delivered to tumor and adjacent healthy tissue at varying pressures (0-1.2 MPa) following intravenous injection of microbubbles (1.00 ± 0.85 µm; 2.4 × 10 microbubbles/100 g). Tissues were collected 24 h post-treatment for histological analysis. Healthy tissue exhibited pressure-dependent damage, including significant differences in red blood cell (RBC) extravasation between 0 and 1.2 MPa conditions (0 ± 0 vs 1.73 × 10 ± 2.15 × 10, p = 0.015), hemorrhagic pools, and tissue disintegration. Conversely, the presence of histopathological features in tumors, regardless of pressure, and no significant differences in RBC extravasation areas between exposure conditions suggests no treatment-induced damage at the tested exposures. These findings indicate F98 gliomas are less sensitive to FUS and microbubbles than healthy spinal cord, likely due to reduced vascularity (p < 0.00001 compared to grey matter, p < 0.05 compared to white matter). This finding indicates alternative strategies (e.g. nanodroplets or molecularly-targeted bubbles) must be explored for effectively treating CNS tumors with low vascularity.