We propose a possible route to achieve high thermoelectric efficiency in molecular junctions by combining a local chemical tuning of the molecular electronic states with the use of semiconducting electrodes. The former allows to control the position of the highest-occupied molecular orbital (HOMO) transmission resonance with respect to the Fermi energy while the latter fulfills a twofold purpose: the suppression of electronlike contributions to the thermopower and the cutoff of the HOMO transmission tails into the semiconductor band gap. As a result a large thermopower can be obtained. Our results strongly suggest that large figures of merit in such molecular junctions can be achieved.