Approximately 20% of intensive care unit (ICU) patients have cancer, and their prognosis has markedly improved in recent years. In addition to improved treatment in the ICU, this is a result of advancements in cancer therapies, including the use of targeted therapies (TTs), such as antibodies and small-molecule kinase inhibitors. Despite the increasing use of TT, there are currently no comprehensive studies examining critically ill cancer patients receiving TT in the ICU. We studied the clinical characteristics of a multicenter cohort of cancer patients who received TT in the ICU. To this end, we extracted data from the iCHOP Registry, comprising critically ill cancer patients from nine centers in Germany and Austria, and analyzed patient characteristics, cancer therapies, and survival outcomes. We then employed Cox proportional hazards regression and Kaplan‒Meier survival analyses to explore factors associated with mortality. Of the 1,762 cancer patients admitted to the ICU who were analyzed for this study, 106 patients (6%) received TT in the ICU, such as antibody-based treatments, kinase inhibitors and proteasome inhibitors. Although the TT recipients were younger, there were several pronounced high-risk features in the TT cohort, as indicated by a greater proportion of hematologic malignancies and autologous stem cell transplantation (SCT), a greater percentage of progressive disease and fewer patients in complete remission at ICU admission than in patients not receiving TT in the ICU. Despite these more pronounced risk features, TT patients had a slightly longer median OS than did the other patients according to Kaplan‒Meier analysis. The factors associated with mortality according to Cox proportional hazards regression analysis included advanced directives, disease progression, SOFA score, invasive mechanical ventilation (IMV), renal replacement therapy, and duration of ICU and hospital stay. Critically ill cancer patients receiving TT in the ICU had distinct characteristics but had comparable survival outcomes compared to patients receiving any other or no antineoplastic therapy in the ICU. While disease status at ICU admission remains crucial, the present study indicates the feasibility and potential benefits of TT in selected ICU patients.