The design of hollow mesoporous nanostructures for cascade catalytic reactions can inject new vitality into the development of nanostructures. In this study, we report a versatile cooperative template-directed coating method for the synthesis of hollow and yolk–shell mesoporous zirconium titanium oxide nanospheres with varying compositions (ZrO₂ content from 0 to 100%), high surface areas (465 m²·g^–1) and uniform mesopores. In particular, the hexadecylamine (HDA) used in the coating procedure serves as a soft template for silica@mesostructured metal oxide core–shell nanosphere formation. By a facile solvothermal treatment route with an ammonia solution and calcination in air, the silica@mesostructured zirconium titanium oxide spheres can be converted into highly uniform hollow zirconium titanium oxide spheres. By simply replacing hard template silica nanospheres with core–shell silica nanocomposites, the synthesis approach can be further used to prepare yolk–shell mesoporous structures through the coating and etching process. The approach is similar to the preparation of mesoporous silica nanocomposites from the self-assembly of the core, the soft template cetyltrimethylammonium bromide (CTAB) and a silica precursor and can be extended as a general method to coat mesoporous zirconium titanium oxide on other commonly used hard templates (e.g., mesoporous silica spheres, mesoporous organosilica ellipsoids, polymer spheres, and carbon nanospheres). The presence of highly permeable mesoporous channels in the zirconium titanium oxide shells has been demonstrated by the reduction of 4-nitrophenol with yolk–shell Au@mesoporous zirconium titanium oxide as the catalyst. Moreover, a cascade catalytic reaction including an acid catalyzed step and a catalytic hydrogenation to afford benzimidazole derivatives can be carried out very effectively by using the accessible acidity of the yolk–shell structured mesoporous zirconium titanium oxide spheres containing a Pd core as a bifunctional catalyst, which makes the hollow zirconium titanium oxide spheres a practicable candidate for advanced catalytic systems.