In the present work, we investigated potential means to obtain neutral tricarbonyl mixed-ligand fac-[M(CO)(3)(LL2)-L-1] complexes (M = Re, Tc-99m) containing the (2-hydroxyphenyl)diphenylphosphine (POH) bidentate ligand ((LH)-H-1) and a series of monodentate ligands (L-2). First, fac[Re(CO)(3)(PO)(H2O)], 1, was synthesized by reaction of POH and [Et4N](2)[Re(CO)(3)Br-3] in equimolar amounts in MeOH at room temperature. Interestingly, with excess of POH this reaction afforded fac-[Re(CO)(3)(PO)(POH)], 2, with POH operating both as a bidentate and as a monodentate ligand. Owing to the presence of the labile aqua ligand, which can be readily replaced by various monodentate ligands, 1 was further used as a precursor to generate a small library of the desired fac-[M(CO)(3)(LL2)-L-1] complexes. Specifically, by reaction of triphenylphosphine (PPh3), imidazole (im), pyridine (py), cyclohexyl isocyanide (cisc), and tert-butyl isocyanide (tbi), the following products were readily obtained in excellent yields (92%-95%): fac-[Re(CO)(3)(PO)(PPh3)], 3, fac-[Re(CO)(3)(PO)(im)], 4, fac-[Re(CO)(3)(PO)(py)], 5, fac-[Re(CO)(3)(PO)(CiSc)], 6, and fac-[Re(CO)(3)(PO)(tbi)], 7. All compounds were fully characterized by elemental analysis, IR and NMR spectroscopies, and electrospray ionization(+) mass spectrometry. Their solid-state structure was elucidated by X-ray crystallography. Of considerable interest is the fact that the corresponding 2'-7' were easily accessible at the Tc-99m-tracer level in quantitative yields after reaction of POH and the respective monodentate ligand L-2 with fac-[Tc-99m(CO)(3)(H2O)(3)] in aqueous MeOH, as verified by comparative chromatographic methods adopting dual photo and radiometric detection modes. The high stability displayed by all Tc-99m complexes during histidine and cysteine challenge assays underscored the suitability of the fac-[M(CO)(3)(PO)L-2] system for radiopharmaceutical development purposes.