Melanoma, a highly aggressive cancer, is closely associated with an elevated tumor mutation burden (TMB) and an active tumor microenvironment (TME). Melanin synthesis, a key feature of melanoma progression, is primarily regulated by tyrosinase (TYR), the rate-limiting enzyme controlled by the microphthalmia-associated transcription factor (MITF). Resveratrol (Res), a natural polyphenol known for its antioxidant and anticancer properties, faces limitations including poor solubility, low bioavailability, and rapid metabolism. To overcome these challenges, a three-dimensional Co(II) coordination polymer {[Co(bpdado)(bpe)(H₂O)₂]·2DMF·2 H₂O}n (1) was synthesized and incorporated into a composite material, 1@CP1, for Res delivery (1@CP1@Res). The system exhibited enhanced solubility, pH-sensitive release, and improved biological activity. Fluorescence assays demonstrated significant quenching in the presence of Cu²⁺ ions, indicating a high sensitivity of 1@CP1@Res to metal ion interactions. The pH-responsive drug release profile was confirmed by in vitro studies showing accelerated release at lower pH values, mimicking the acidic tumor microenvironment. Cell viability assays revealed that 1@CP1@Res significantly inhibited the proliferation of murine B16-F10 melanoma cells, with cell survival rates of 72.4%, 58.2%, and 43.6% at 24, 48, and 72 h of incubation, respectively, at a concentration of 100 µM. Molecular docking studies further revealed multiple binding interactions between Res and the coordination polymer, suggesting a promising therapeutic strategy for melanoma treatment by integrating advanced materials with bioactive compounds.