Janus nanostructures that possess two or more distinct components and surface functions have attracted more and more attention. Here, we present a seed-shape defined growth mechanism for the preparation of anisotropic Janus nanostructures, in which the shape of periodic mesoporous organosilica (PMO) is determined by the shape of Au nanoparticles. Various shaped Au@PMO composite nanostructures, such as rods, spheres, and plates, are prepared based on this general growth mechanism. By adjusting the reaction parameters (temperature, surfactant), various shaped AuNR@PMO Janus nanostructures, including horsebean- and fingernail-like nanostructures, have been successfully prepared. We also demonstrate the potential applications of such composite nanostructures. As an example, the as-prepared rod-like Janus Au@PMO nanostructures show great performance in chemo-photothermal combination therapy because of the excellent photothermal effect of Au nanorods and the high surface area of PMO nanorods. This research may open a new direction to the controllable synthesis and practical application of dedicated nanostructures with desired properties.