It is generally assumed that the hydrothermal stability of organically modified silica networks is promoted by high monomer connectivity, network flexibility, and the presence of hydrophobic groups in the network. In this study a range of organosilica compositions is synthesized to explore the extent to which these factors play a role in the hydrothermal dissolution of these materials. Compositions were synthesized from hexafunctional organically bridged silsesquioxanes (OR1)3Si–R–Si(OR1)3 (R = −CH2–, –C2H4–, –C6H12–, –C8H16–, –p-C6H4–; R1 = −CH3, –C2H5), tetrafunctional (OEt)2Si(CH3)–C2H4–Si(CH3)(OEt)2 and Si(OEt)4, trifunctional silsesquioxanes R′-Si(OMe)3 (R′=CH3, n-C3H7, cyclo-C6H11, phenyl), and bifunctional Si(i-C3H7)2(OMe)2. The bond strain, connectivity and hydroxyl concentration of all networks were estimated using 29Si cross-polarized magic angle spinning nuclear magnetic resonance and Fourier-transform infrared spectroscopy. The hydrophilicity was characterized by monitoring the water uptake of the materials in moisture treatments with thermogravimetric analysis, differential scanning calorimetry, and Fourier-transform infrared spectroscopy. The resistance of each network against hydrothermal dissolution in a water/1,5-pentanediol mixture at 80 °C and pH 1, 7, and 13 was analyzed with inductively coupled plasma optical emission spectroscopy and X-ray fluorescence. Bond strain appears to significantly increase the tendency to dissolve under hydrothermal conditions. The stabilizing influences of increased connectivity and hydrophobicity were found to be weak.