Abstract: Revealing the fundamental mechanisms governing reactant-induced disintegration of supported metal nanoparticles and their dependences on the metal component and reactant species is vital for improving the stability of supported metal nanocatalysts and single-atom catalysts. Here we use first-principles-based disintegration thermodynamics to study the CO- and OH- induced disintegration of Ag, Cu, Au, Ni, Pt, Rh, Ru, and Ir nanoparticles into metal-reactant complexes (M(CO)_n, M(OH)_n, n=1 and 2) on the pristine and bridge oxygen vacancy site of TiO₂(110). It was found that CO has a stronger interaction with these considered transition metals compared to OH, resulting in lower formation energy and a larger promotion effect on the disintegration of nanoparticles (NPs). The corresponding reactant adsorption energy shows a linear dependence on the metal cohesive energy, and metals with higher cohesive energies tend to have higher atomic stability due to their stronger binding with reactant and support. Further disintegration free energy calculations of NPs into metal-reactant complexes indicate only CO-induced disintegration of Ni, Rh, Ru, and Ir nanoparticles is thermodynamically feasible. These results provide a deeper understanding of reactant-induced disintegration of metal nanoparticles into thermodynamically stable metal single-atom catalysts.