The incorporation of living cells into solid-state platforms or devices is important for a diverse range of applications including tissue engineering, array-based drug discovery, bio-sensing, and the powering of nanodevices. Here we report a cell-directed assembly approach to the 3-D incorporation of Saccharomyces cerevisiae in a uniformly nanostructured inorganic host that maintains cell accessibility, addressability, and viability in the absence of an external fluidic architecture. Using in-situ grazing incidence small angle x-ray scattering (GISAXS), along with transmission electron microscopy (TEM) and laser scanning confocal imaging, we investigated how amphiphilic phospholipids direct the formation of ordered biocompatible silica mesophases in the absence or presence of S. cerevisiae. We find that living S. cerevisiae profoundly alter the self-assembly pathway, each cell creating around itself an extensive multilayered phospholipid vesicle that interfaces coherently with the nanostructured silica host, while the cells collectively control the development of the surrounding nanostructure. We also demonstrate the ability of S. cerevisiae to rapidly and efficiently organize nanocrystals and proteins within their surrounding multilayered lipid vesicles, suggesting a new general synthetic approach wherein cells direct their self-integration into functional 3D hierarchical/multiscale devices. This new interaction of cells with nanomaterials has been termed cell-directed assembly (CDA), as its features are only observed in the presence of living cells. To enhance the flexibility of the system, we have developed a new approach in which living cells are added to pre-assembled, phospholipid-templated silica nanostructures. The cells are able to integrate themselves into the nanostructure in a manner that preserves many of the key features of cell-directed assembly.