Manipulation of micro/nano particles has been well studied and demonstrated by optical, electromagnetic, and acoustic approaches, or their combinations. Manipulation of internal structure of droplet/particle is rarely explored and remains challenging due to its complicated nature. Here we demonstrated the manipulation of internal structure of disk-in-sphere endoskeletal droplets using acoustic wave for the first time. We developed a model to investigate the physical mechanisms behind this novel phenomenon. Theoretical analysis of the acoustic interactions indicated that these assembly dynamics arise from a balance of the primary and secondary radiation forces. Additionally, the disk orientation was found to change with acoustic driving frequency, which allowed on-demand, reversible adjusting disk orientations with respect to the substrate. This novel dynamic behavior leads to unique reversible arrangements of the endoskeletal droplets and their internal architecture, which may provide a new avenue for directed assembly of novel hierarchical colloidal architectures and intracellular organelles or intra-organoid structures.