BACKGROUND Transarterial radioembolization (TARE) is a locoregional minimally invasive therapeutic strategy to treat primary and secondary hepatic neoplasia. OBJECTIVE The objective was to assess TARE-induced immuno-oncological effects and its perspective for potential therapy improvement by using a combinatory strategy with immune checkpoint inhibitors (ICI). RESULTS Yttrium-90 (90Y) TARE is used in patients with persisting liver function as the first- and second-line treatment for cholangiocarcinoma and hepatocellular carcinoma and chemotherapy refractory liver metastasis of different primaries. Combination therapy with 90Y TARE and ICI may synergistically improve antitumoral immunity and patient outcome. Currently, there are no clinical studies with published data regarding this combination therapy and the subsequently induced immunological effects. Clinical data on other isotopes, e.g., holmium-166 (166Ho), are also lacking. CONCLUSIONS The clinical evidence of combined treatment with TARE and ICI must be considerably improved. This innovative therapy concept must be studied in new trials assessing the immunological data, including cellular phenotypes, activation, functions, and biomarkers. This may provide valid, sensitive, and specific models in order to evaluate the optimal therapy concept and/or the therapy combination for the best patient outcome.