Quantum and nonquantum descriptors clearly related to physicochemical features and predictors of the trends to evolve along different stages of a known mechanism of action were determined for a set of square-planar compounds of general formula [M(II)A(1)A(2)L(1)L(2)] (M(II) = Pt(II)/Pd(II); A(i)/L(i) = carrier/labile ligands), structurally related to the anticancer agent Cisplatin. Selected compounds have been sorted and classified by Ward's Cluster Analysis and Principal Components Analysis data-mining techniques using seventeen 1D and two 3D of such theoretical descriptors calculated at the DFT level (PCM-B3LYP/LANL2DZ/6-31G*). A rationale emerging from the study is that whereas most significant differences come from substitution of Cisplatin ligands, cis/trans isomerism, and exchange of M(II) introduce minor alterations in the electronic/geometrical structure. This provides theoretical support to the assay of transplatinum compounds as potential anticancer drugs, a fact already pointed out by empirical evidence. Similarly, the little geometrical/electronic differences triggered by switching M(II) from Pt to Pd enable us to devise a rational path to propose new compounds with expected good anticancer profiles, tuning alterations introduced by simultaneously changing both metal and ligands. Current results serve thus to enlarge the Cleare-Hoeschele guides for Pt(II) square-planar anticancer potential drugs to Pd(II) compounds, both using cis/trans scaffolds.