Multi-cation substituted pyrochlores are potential matrices for immobilization of long-lived high level nuclear waste. In this paper, we report, the structural and thermodynamic stabilities of aliovalent multi cation substituted Gd₂Ti₂O₇ pyrochlore compounds determined by experimental and theoretical methods. A series of cubic pyrochlore-type Gd_2-2xCa_xZr_xTi₂O₇ (0.0  ≤ x  ≤ 0.4) compounds were synthesized and characterized by XRD and Raman spectroscopy techniques. It is observed that incorporation of Ca²⁺ and Zr⁴⁺ at Gd³⁺ site does not significantly alter crystal lattice of Gd₂Ti₂O₇. Calorimetric studies were carried out to determine the thermodynamic stability of Gd_2-2xCa_xZr_xTi₂O₇ compounds. The observed data indicate that standard molar enthalpy of formation of Gd_2-2xCa_xZr_xTi₂O₇ decreases steadily with increasing dopant concentration which has been attributed to increasing distortion of the polyhedra around the cations. These inferences were further supported by DFT calculations.