Solvation of biomolecules by a hydrophilic and hydrophobic environment strongly affects their structure and function. Here, the structural, vibrational, and energetic properties of size-selected clusters of the micro-hydrated tryptamine cation with N-2 ligands, TRA(+)-(H2O)(m)-(N-2)(n), (m,n <= 3), are characterized by infrared photodissociation spectroscopy in the 2800-3800 cm(-1) range and dispersion-corrected density functional theory calculations at the omega B97X-D/cc-pVTZ level to investigate the simultaneous solvation of this prototypical neurotransmitter by dipolar water and quadrupolar N-2 ligands. In the global minimum structure of TRA(+)-H2O generated by electron ionization, H2O is strongly hydrogen-bonded (H-bonded) as proton acceptor to the acidic indolic NH group. In the TRA(+)-H2O-(N-2) clusters, the weakly bonded N-2 ligands do not affect the H-bonding motif of TRA(+)-H2O and are preferentially H-bonded to the OH groups of the H2O ligand, whereas stacking to the aromatic pi electron system of the pyrrole ring of TRA(+) is less favorable. The natural bond orbital analysis reveals that the H-bond between the N-2 ligand and the OH group of H2O cooperatively strengthens the adjacent H-bond between the indolic NH group of TRA(+) and H2O, while pi stacking is slightly noncooperative. In the larger TRA(+)-(H2O)(m) clusters, the H2O ligands form a H-bonded solvent network attached to the indolic NH proton, again stabilized by strong cooperative effects arising from the nearby positive charge. Comparison with the corresponding neutral TRA-(1120), clusters illustrates the strong impact of the excess positive charge on the structure of the microhydration network.