In this paper, we show how the thermoelectric properties can be modified in crystallographic structures based on the CdI2 type layer, by changing the block layers between these CdI2 type layers or by going from oxides to selenides and sulfides. In the case of oxides, the unique properties generated in these structures will be demonstrated in Bi-based misfit compounds. By combining Hall effect, resistivity, and Seebeck coefficients in single crystals of this family, the importance of doping and of spin and orbital degeneracy term on the Seebeck coefficient will be shown. From this single crystal investigation, the power factor at 300 K is found to be unexpectedly constant as a function of doping. To further enhance the power factor and thus ZT, it is necessary to modify either the block layer or to perform anionic substitutions. By going from oxides to selenides and sulfides, the decrease of the ionic character can induce a decrease of electrical resistivity. Compared to oxides, the properties can generally be described in a more classical way using Boltzmann transport theory. For these materials, the critical parameter is then thermal conductivity and this quantity can be decreased as shown here by intercalating Cu between the layers (CuxTiS2), or by making solid solution such as TiS2 − xSex. These two approaches will be described here, leading to ZT close to 0.5 and 0.4, at 800 and 700 K, respectively.