Hosts of 2D materials exist, yet few allow compositional and structural tailoring as the MQ₂ (M = Mo, W; Q = S, Se) family does, for which various structural superlattices have been synthesized. Using thorough first-principles calculations, we show how bonding hierarchy contributes to the structural resilience of 2D PdPQ and allows for full-range alloying of sulfur and selenium. Within the structural unit of Pd₂P₂Q₂, the covalently-bonded [P₂Q₂]⁴⁻ polyanions hold the structure together with their molecular-like P–P bonds while ionically bonded Pd–Qs allow the S/Se substitution. Here, the bonding hierarchy imparts superior electronic and structural features to the PdPQ monolayers. As such, the flat-and-dispersive valence band and the eight degenerate valleys of the conduction band benefit the p-type and n-type thermoelectricity of pristine PdPQ, which can be further enhanced by alloying. The high-entropy alloying synergistically suppresses the lattice heat transport from 75 to 30 W m⁻¹ K⁻¹ and increases the band degeneracy of PdPQ monolayers, resulting in an overall improvement in zT. Combining these features, in a naïve approach, results in a large zT approaching two for both p-type and n-type doping. However, accurate fully-fledged electron–phonon calculations rebut this promise, showing that at high temperatures, the increased electron scattering results in a stagnant power factor in the flat-and-dispersive valence band. Using a realistic first-principles scattering, we finally calculate the thermoelectric efficiency of PdPQ (Q = S, Se) and highlight the importance of an accurate estimation of electron relaxation time for thermoelectric predictions.