<p>Objective: To characterize the anatomical patterns of skull base involvement by malignant tumors and to evaluate the surgical approaches utilized in a single-center cohort. Methods: Clinical records and imaging data of 15 patients who underwent surgical resection for skull base involvement from malignant tumors between November 2004 and June 2020 were retrospectively reviewed. Primary tumor origin, patterns of involvement, surgical approaches, and surgical outcomes were analyzed. Results: The sellar–clival complex was the most commonly affected region (12/15, 80.0%), predominantly in cases of renal cell carcinoma, nasopharyngeal carcinoma, and thyroid carcinoma. Additional involved sites included the paranasal sinuses (4/15, 26.7%), petrous apex (4/15, 26.7%), cavernous sinus (3/15, 20.0%), infratemporal fossa (3/15, 20.0%), occipital bone (2/15, 13.3%), jugular foramen (1/15, 6.7%), and cerebellopontine angle (1/15, 6.7%). Gross total resection (GTR) was achieved in 11 patients (73.3%), all of whom experienced symptomatic improvement. Postoperative complications included facial paralysis, visual deterioration, and carotid artery rupture. Over a mean follow-up of 55.9 months, 10 of the 11 patients who achieved GTR remained free of local progression, although systemic disease progression accounted for several deaths. Five patients died during the follow-up period. Conclusion: This study outlines the anatomical distribution of skull base involvement from malignant tumors, which appears to align with putative lymphatic-like drainage pathways. Minimally invasive approaches—such as endoscopic endonasal, transoral, and infratemporal routes—are viable options for selected patients, providing effective local control while limiting surgical morbidity. Clinical trial number: Not applicable.</p>