AbstractAu^I‐carbene and Pt^IV−Au^I‐carbene prodrugs display low to sub‐μM activity against several cancer cell lines and overcome cisplatin (cisPt) resistance. Linking a cisPt‐derived Pt^IV(phenylbutyrate) complex to a Au^I‐phenylimidazolylidene complex2, yielded the most potent prodrug. While in vivo tests against Lewis Lung Carcinoma showed that the prodrug Pt^IV(phenylbutyrate)‐Au^I‐carbene (7) and the 1 : 1 : 1 co‐administration of cisPt: phenylbutyrate:2efficiently inhibited tumor growth (≈95 %), much better than2(75 %) or cisPt (84 %),7exhibited only 5 % body weight loss compared to 14 % for2, 20 % for cisPt and >30 % for the co‐administration.7was much more efficient than2at inhibiting TrxR activity in the isolated enzyme, in cells and in the tumor, even though it was much less efficient than2at binding to selenocysteine peptides modeling the active site of TrxR. Organ distribution and laser‐ablation (LA)‐ICP‐TOFMS imaging suggest that7arrives intact at the tumor and is activated there.