One-step cranioplasty combined with tumor removal is a recognized approach in neuro-oncology for patients with neoplastic skull invasion. The use of advanced technologies, including Mixed Reality (MR), has introduced new possibilities in surgical workflows. MR technology may provide additional benefits in preoperative planning, patient engagement, and intraoperative guidance. Can the proposed treatment algorithm, which includes Mixed Reality (MR) for preoperative planning and intraoperative navigation, demonstrate tangible utility and improve outcomes in the surgical management of skull-invasive tumors? A retrospective study was conducted on 14 patients treated at Cannizzaro Hospital, Catania, Italy, for skull-invasive tumors. The treatment algorithm incorporated tumor removal and one-step cranioplasty using custom-made titanium alloy meshes. Standard intraoperative navigation was compared with MR-based navigation. MR headsets and the Virtual Surgery Intelligence (VSI) platform were employed for preoperative planning, surgical guidance, and patient/family communication. Tumor types included nine meningiomas and five other tumor variants. The integration of MR proved beneficial for preoperative planning, facilitating enhanced visualization of patient anatomy and aiding communication with patients and families. MR-assisted intraoperative navigation offered improved anatomical familiarity but demonstrated slightly lower accuracy compared with standard navigation. Postoperative outcomes were satisfactory across the cohort, with no significant complications reported. The study highlights the potential utility of the proposed treatment algorithm including MR technology in the surgical management of skull-invasive tumors. While MR provides enhanced visualization and preoperative engagement, standard navigation remains more precise during surgery. Nevertheless, MR serves as a valuable complementary tool, and its role in neuro-oncological workflows is expected to grow with technological advancements.