Idarubicin (IDA) is the analog of daunorubicin (DNR). The absence of the methoxy group at position 4 of IDA remarkably improved lipophilicity, which is responsible for extra cellular uptake, higher DNA-binding ability, and considerable cytotoxicity in correlation with doxorubicin (DOX) and DNR. In this paper, we conceived two principal objectives: we realized the crystal structure of IDA by X-ray diffraction measurements on single crystals at room temperature (monoclinic, space group P2 1 , a = 5.1302(2) Å, b = 9.9122(5) Å, c = 24.8868(11) Å; β = 91.425(4)°; V = 1265.14(10) Å 3 ) with refinements of the structure converged to the final R = 3.87%. The second objective has been to develop gold nanoparticles encapsulated with idarubicin through an original methodology in which gold salt (HAuCl 4 ) is chelated with IDA and diacid polymer (PEG) to form hybrid nanoparticles called IDA IN PEG-AuNPs in which drug solubility was enhanced. The computational studies were in agreement with the experimental observations. These hybrid nanoparticles and their precursors were analyzed by Raman, UV−Vis, 1 H NMR, and transmission electron microscopy (TEM). The main results are completed by a theoretical approach to understand the whole process.