The results of a X-ray photoelectron spectroscopy (XPS) and steady-state absorption spectroscopy study of the electronic structure, and cationic and excited states of a series of 1,3,5,7-tetramethyl-substituted BODIPYs (4Me,2R-BODIPYs) are presented. The experimental data were interpreted using high-level ab initio quantum chemical computations, including the algebraic diagrammatic construction method for the polarization propagator of the second order (ADC(2)), the outer-valence Green's function (OVGF) method, the density functional (DFT) approach, and the time-dependent DFT (TD-DFT) approach. Substitution effects on the XPS and absorption spectra were determined for 2,6-positions of 4Me,2R-BODIPY pyrrole nuclei (R = H, Br, Bu, benzyl). A very satisfactory performance of the DFT Koopmans theorem analogue was demonstrated with respect to the energy intervals between the electronic levels of 4Me,2R-BODIPY above 13 eV (BHHLYP functional) and the values of the HOMO-LUMO energy gap (ωB97X functional).