Room-temperature phosphorescence (RTP) materials have widespread applications in biological imaging, anticounterfeiting, and optoelectronic devices. Because of the predesignability of metal-organic complexes (MOCs), the RTP materials based on MOC systems have received huge attention from researchers. The coordinate anchoring of luminophores to enhance the rigidity of organic molecules and restrict the nonradiative transition offers opportunities for generating MOC materials with captivating RTP performance. Hitherto, most of the MOC-based RTP materials feature a single luminophore ligand. The development of new MOC systems with RTP functionality is still challenging. Herein, we use the mixed-ligand synthetic strategy to produce isostructural MOCs, [Zn(TIMB)(X2-TPA)]·H2O (1, X = Cl; 2, X = Br; TIMB = 1,3,5-tris(2-methyl-1H-imidazol-1-yl)benzene; H2-X2-TPA = 2,5-dichloroterephthalic and 2,5-dibromoterephthalic acid), and modulate the RTP properties of resultant products via the synergy of coordinate anchoring and substitution synthesis. 1 and 2 feature similar coordination layers composed of neutral TIMB and anionic X2-TPA2- ligands, which provide a good structural model to tune the RTP performances of final products via substitution synthesis. Different from the reported RTP materials based on MOC systems, our study provides a general way to build and modulate MOC-based RTP materials with the assistance of coordinate anchoring and substitution synthesis strategies.