Understanding the role of metal ions in living organisms and their interactions with biological compounds is fundamental for our health and for developing technological devices for bioinorganic applications. In this work, structural aspects and photophysical mechanisms involved in the luminescence of the Zn(II)-guanine complex in water were studied by using computational quantum chemical methods, providing molecular-level explanations for reported experimental findings. Structural aspects were investigated with def2-SVP basis sets, Density Functional Theory, Resolution of Identity Algebraic Diagrammatic Construction in Second-Order (RI-ADC(2)), Polarizable Continuum Model (PCM), and Conductor-like Screening Model (COSMO) methods. Spectroscopic properties and photophysical deactivation mechanisms were explored with the atomic natural orbital basis sets including relativistic and semicore correlation (ANO-RCC-VDZP) basis sets, Multistate Complete-Active-Space Second-Order Perturbation Theory (MS-CASPT2), and Polarizable Continuum Model (PCM) methods. Our results indicate that Zn(II) ions bind preferentially to the N7 position, and three water molecules in its coordination sphere are sufficient for describing the photophysical properties. The complexation with Zn(II) ions and solvation effects favor fluorescence because the minimum energy region of the S1 (La) (1ππ*) ((La)min) potential energy hypersurface is stabilized, the (La/GS) crossing region is destabilized, and a high energetic barrier along the pathway from the (La)min and (La/GS) regions hampers fast nonradiative return of the electronic population to the ground state, as observed for isolated 9H-guanine.