<p>Cross-conjugated dienones of the cycloalkanone series containing donor groups are D-π-A-π-D type dyes and, therefore, they are widely used as fluorophores, fluorescent probes, and photosensitizers. The structure and properties of promising cyclobutanone-based dienones were modeled and the efficiency of the (<i>E</i>,<i>E</i>)—(<i>E</i>,<i>Z</i>) isomerization, which is inherent in this class of compounds, was studied. The influence of the orientation of substituents in the benzene ring on the energy and probability of lower radiative transitions and on the barrier on the energy surface of the S₁ state, which directs deactivation to either radiative or non-radiative pathway through isomerization, was analyzed. For <i>ortho</i>-substituted dienones with strong electron-donating substituents, the calculation predicts an intense absorption band in the visible region and high fluorescence quantum yields. Therefore, these compounds may be of interest for the design of new fluorophores based on cross-conjugated dienones. Modifications of the molecular structure of dienones by introducing linkers between the electron-donating group in the <i>ortho</i>-position of the benzene ring and the methine carbon atom were considered. The presence of a conformationally rigid linker increases the efficiency of the lower radiative transitions. An increase in the rigidity of the conjugated system of <i>ortho</i>-substituted dienones does not increase the fluorescence efficiency.</p>