We performed density functional theory-based calculations to investigate the structural, electrical and thermal properties of transition-metal dichalcogenides (TMDs). Two-dimensional TMDs are of broadening research interest due to their novel physical, electrical, and thermoelectric properties. Having the chemical formula MX2, where M is a transition metal and X is a chalcogen, there are many possible combinations to consider for materials-by-design exploration. We investigated the structure, electronic, and phonon properties of eighteen different TMD MX2 materials compositions as a benchmark to explore the impact of various elements. Our results identified key factors, including atomic weight, radius, oxidation state and interfacial lattice mismatching, to optimize MX2 compositions for desired thermoelectric performance. We also added substitutional dopants and created heterojunctions in the TMD materials to enhance their thermoelectric properties. We will present a new computational screening approach to draw correlation among the physical properties of constituent transition metals, substitutional dopants, heterojunctions, and resultant 2D-TMDs.