The Zintl phase solid-solution Ca11-xYbxSb10-yGez (0 <= x <= 9; 0 <= y <= 3; 0 <= z <= 3) system with the cationic/anionic multisubstitution has heen synthesized by molten Sn metal flux and arc-melting methods. The crystal structure of the nine title compounds were characterized by both powder and single-crystal X-ray diffractions and adopted the Ho11Ge10 type structure with the tetragonal space group 14/mmm (Z = 4, Pearson. Code tI84). The overall isotypic structure of the nine title compounds can be illustrated as an assembly of three different types of cationic polyhedra sharing faces with their neighboring polyhedra and the three-dimensional cage-shaped anionic frameworks consisting of the dumbbell-shaped Sb-2 units and the square-shaped Sb-4 or (Sb/Ge)(4) units. During the multisubstitution trials, interestingly, we observed a metal-to-semiconductor transition as the Ca and Ge contents increased in the title system from Yb11Sb10 to Ca9Yb2Sb7Ge3 (nominal compositions) on the basis of a series of thermoelectric property measurements. This phenomenon can be elucidated by the suppression of a bipolar conduction of holes and electrons via an extra hole-carrier doping. The tight-binding linear muffs-tin-orbital calculations using four hypothetical structural models nicely proved that the size of a pseudogap and the magnitude of the density of states at the Fermi level are significantly influenced by substituting elements: as well as their atomic sites in a unit cell. The observed particular cationic/anionic site preferences, the historically known abnormalities of atomic displacement parameters, and the occupation deficiencies of particular atomic sites are further rationalized by the QVAL value criterion on the basis of the theoretical calculations. The results of SEM, EDS, and TGA analyses are also provided.