In this work, for the first time, we show that trabectedin-olaparib combination activates the cGAS-STING pathway, leading to a double-edged effect in sarcoma cells: it increases the fraction of OCT4+ cells and the expression of NKG2DLs, eventually enhancing NK/CIK antitumor activity against both bulk and OCT4+ persistent sarcoma cells. Here, STING1 is linked to sarcoma.