Cancer is the second-leading cause of death in developed societies. Specifically, cancers of the spine and brain come with significant therapeutic challenges. Chordomas are semi-malignant tumors that develop from embryonic residuals at the skull base (clival) or coccyx (sacral). Small tumor fragments can remain in the operation cavities during surgical resection, forming new tumor sites. This requires repeated surgeries or the application of proton-beam radiation and chemotherapy, which often do not lead to complete remission of the tumors. Hence, there is a need for novel therapeutic avenues that are not limited to killing visible tumors but can be applied after surgery to decrease chordoma recurrences. Reactive oxygen species (ROS) generated locally via novel medical gas plasma technologies are one potential approach to address this clinical problem. Previously, broad-spectrum free radicals generated by these cold physical plasmas operated at about body temperature were shown to oxidize cancer cells to the disadvantage of their growth and induce immunogenic cancer cell death (ICD), ultimately promoting anticancer immunity. This review outlines the clinical challenges of chordoma therapy, how medical gas plasma technology could serve as an adjuvant treatment modality, and potential immune-related mechanisms of action that could extend the longevity of gas plasma therapy beyond its acute local tissue effects.