The electronic and charge transport properties of four derivative groups containing nineteen different tetrathiafulvalene (TTF) and tetrathiapentalene (TTP) derivative compounds were theoretically investigated by density functional theory (DFT) based on the Marcus–Hush theory. In particular, we have considered TTF or TTP systems where some hydrogen atoms are substituted with methoxy or halogen moieties since it is well known that these electron-withdrawing groups are used to reduce the energies of frontier orbitals (HOMO and LUMO) and to increase the stability of the TTF derivative. A comparative analysis of the crystal structures reveals that the face-to-face layer structure and the herringbone structure with slip-stacks of the dimers exhibit higher charge transfer values compared with the disordered structures, and that the face-to-face π–π interaction and S–S interactions are favorable for molecular stacking and charge transport behavior. The computed values of the transfer integrals show that variation in calculated transfer integral values is likely along specific directions corresponding to the π–π stacking degree of the molecules. The interface charge conduction mechanism between two different molecule crystals is investigated, and we find there are high-conducting interfaces and low resistances of about 10–50 kΩ. Furthermore, the calculated data demonstrate that the TTF derivatives should be candidates for high-performance organic materials with high mobility values and good stability, and that the predicted highest hole and electron mobility values are 1.821 cm² V⁻¹ s⁻¹ and 1.709 cm² V⁻¹ s⁻¹, respectively, at 300 K. The high mobility combined with simple processing make TTF derivatives promising candidate materials for electronic devices where low cost and flexibility are required.