Nanostructured titanosilicate materials based upon interfacing nano-TiO₂ with nano-SiO₂ have drawn much attention due to their huge potential for applications in a diverse range of important fields including gas sensing, (photo)catalysis, solar cells, photonics/optical components, tailored multi-(bio)functional supports and self-cleaning coatings. In each case it is the specific mixed combination of the two SiO₂ and TiO₂ nanophases that determines the unique properties of the final nanomaterial. In the bulk, stoichiometric mixing of TiO₂ with SiO₂ is limited by formation of segregated TiO₂ nanoparticles or metastable glassy phases and more controlled disperse crystalline mixings only occur at small fractions of TiO₂ (<15 wt%). In order to more fully understand the stability of nano-SiO₂ and nano-TiO₂ combinations with respect to composition and size, we employ accurate all-electron density functional calculations to evaluate the mixing energy in (Ti_xSi_1−xO₂)_n nanoclusters with a range of sizes (n = 2–24) having different titania molar fractions (x = 0–1). We derive all nanoclusters from a dedicated global optimisation procedure to help ensure that they are the most energetically stable structures for their size and composition. We also consider a selection of representative intimately mixed crystalline solid phase (Ti_xSi_1−xO₂)_bulk systems for comparison. In agreement with experiment, we find that homogeneous mixing of SiO₂ and TiO₂ in bulk crystalline phases is energetically unfavourable. Conversely, we find that SiO₂–TiO₂ mixing is energetically favoured in small (Ti_xSi_1−xO₂)_n nanoclusters. Following the evolution of mixing energy with nanocluster size and composition we find that mixing is most favoured in nanoclusters with a diameter of 1 nm with TiO₂ molar fractions between 0.3–0.5. Thereafter, mixed nanoclusters with increasing size have progressively less negative mixing energies up to diameters of approximately 1.5 nm. We propose some chemical-structural principles to help rationale this energetically favourable nanoscale mixing. As a guide for experimentalists to observe and characterize these mixed nano-species we also provide two measurable signatures of mixing based on their unique vibrational and structural characteristics.