Inorganic/organic hybrids have great potential for the production of bioactive scaffolds which have tailored mechanical properties and degradation rates suitable for tissue engineering. For bone regeneration, calcium incorporation into hybrids at low temperatures is important due to its ability to stimulate new bone formation. As a consequence, understanding the homogeneity of the critical inorganic and organic components will be the key to the development of such hybrids. The aim of this interdisciplinary study was to use time-of-flight secondary ion mass spectrometry (ToF-SIMS) to determine the homogeneity of these critical components. We evaluated various sol–gel silica/γ-polyglutamic acid (γ-PGA) hybrid systems produced using different routes to introduce the calcium, thereby tailoring and optimizing hybrid syntheses and processing routes. Dimethyl carbonate (DMC) was used to improve the inorganic/organic coupling and its influence on the homogeneity of the hybrid structures was also examined. The results revealed that the calcium salt form of γ-PGA was promising for calcium incorporation since homogeneous products could be obtained. The ToF-SIMS data also indicated that the reaction time of hybrid synthesis and the timing of the addition of DMC can affect the homogeneity of hybrids.