Incidence and prevalence of most types of cancers are continuously rising. Oncological research progresses as well, with many new drugs and treatment modalities launched in the last years. Cold physical plasma is a promising new technology for oncology, and already applied in many cancer models successfully. First tumor patients benefited from plasma therapy in the palliative setting. While superficial tumors provide an excellent treatment target for repetitive plasma treatment, tumors within the bodies are much are harder to reach. Plasma treatment can be envisioned during radical surgery to treat wound margins often harboring micrometastasis but plasma intervention may be limited to a single application in such setting. Moreover, diffuse metastatic spread throughout the entire body is unlikely to be reached with plasmas at all. A conceptual paradigm from the field of immunology is that cancer cells are visible to the immune system. They are seen as “foreign” because of mutated proteins and therefore peptide sequences presented on major histocompatibility complexes on the cell surface presented to T cells, which in turn aid in killing cancer cells. However, tumor cells evolve to hide their immunogenic potential. This can be retrieved by immunogenic cancer cell death (ICD) induced with, e.g., anthracyclines treatment. A number of physical therapies are ICD inducers as well (radiation, photodynamic therapy), and cold plasma was suggested to be added to this list. The vision of using plasmas as immune modulators is elegant because it would provide cancer patients with an endogenous weapon (the immune system) to battle cancer not only locally but systemically. This may also work in a vaccination approach together with autologous dendritic cells, as there have been many efforts with tumor cell vaccination already in cancer immunotherapy already. This talk will focus on recent advances in plasma oncology and drafts key challenges and research strategies crucial for plasmas as adjuvant oncotherapy in future.