Quaternary chalcogenides composed of earth-abundant and primarily nontoxic constituents are currently being explored for thermoelectric applications. The representatives of this class, CuZn2InTe4 and AgZn2InTe4, have been synthesized, and here, we present a comparative study of their structure-property relations using first principles simulations. Our calculations show that the lattice structure for both materials is very similar in terms of characteristic atomic distances and lattice structures, which compare well with experimental data. The electronic structure results indicate that both materials are direct gap semiconductors whose electron localization and charge transfer properties reveal polar covalent bonding in the lattice. The calculated phonon structure shows dynamic stability with unique vibrational properties for each material.