Several quinary Zintl compounds belonging to the Ca_5−xYb_xAl₂Sb_6−yGe_y (1.0 ≤ x ≤ 1.5, 0.2 ≤ y ≤ 0.8) solid-solution system have been synthesized by arc-melting and characterized by both powder and single-crystal X-ray diffractions. The initially synthesized Ge-doped Yb-rich compounds successfully underwent the structural transformation from the Ba₅Al₂Bi₆-type to Ca₅Ga₂Sb₆-type phase via the post-heat treatment at 1023 K for 2 weeks. The targeted Ge-doped Ca₅Ga₂Sb₆-type phase adopts the orthorhombic space group Pbam (Z = 2, oP26) with seven independent asymmetric atomic sites in a unit cell, and the enhanced zT value of this product implied the hole doping was successfully applied in part. More interestingly, during the investigation for an observed cationic site-preference, which could be accessed by the size-factor based on the size match between a central atom and the site volume, and the electronic-factor based on the QVAL values, we revealed that the observed structural transformation of the title system from the Ba₅Al₂Bi₆-type to Ca₅Ga₂Sb₆-type phase should be caused by the migration of cations from the kinetically favorable sites to the thermodynamically more favorable sites during the post annealing process. To verify this experimental observation, a series of theoretical studies based on the “coloring-problem” was performed using three different model structures, and the detailed site energies and bond energies were thoroughly investigated.