Smart porous silica–polymer nanomaterials provide a very versatile platform for simultaneous diagnostic and smart therapeutic applications, or theranostics. Nanocarriers for this application should be able to deliver their cargo on-demand at the desired location and provide diagnostic information on their position. To this end, they should accommodate a large cargo payload, be traceable, feature targeting groups that direct them to the desired location, and be equipped with a smart release control mechanism that delivers the cargo at that location. Their ultimate objective is to use the diagnostic information acquired locally to control the therapeutic action, either by a self-controlled mechanism or by an external trigger. Here, we focus on the use of hybrid mesoporous silica nanoparticles that combine therapeutic and diagnostic functionalities, presenting the synthetic versatility they offer and a number of applications in controlled delivery in the biomedical field.