In this thesis we use a combination of density functional theory and equilibrium Green’s function to study thermoelectricity in molecular scale. We have aimed to improve the efficiency of single molecules in converting heat to electricity by carefully designing them. We introduced a novel strategy for designing molecules with low thermal conductance. This strategy states that adding side branches of different length to the backbone of a molecule can eliminate phonon transport through the backbone over a wide range of frequencies. Moreover, we demonstrate that chemical modification of thiophene molecular wire to ethylenedioxy-thiophene molecular wire can improve their thermoelectric efficiency. Furthermore, to demon- strate that the adopted molecular designs will be effective when scaled up to a self-assembled monolayer (SAM) of molecules, we model three independent exper- iments on gold-SAM-graphene vertical transport devices. The agreement between our calculations and the experiments elucidates the survival of quantum interfer- ence effect on a single molecular level in SAM devices. The work presented in this thesis has received considerable attention from many experimental groups in the UK and overseas stimulating novel experimental studies which are ongoing at present.