Blueberry pomace is a polyphenol-rich by-product of fruit processing. A face-centered central composite design (FCCCD) optimized hydroethanolic extraction across time (20–60 min), temperature (20–60 °C) and ethanol (20–80%), evaluating total phenolic content (TPC), yield and selectivity. The selected condition (40 min, 60 °C, 50% ethanol) reached 20.0 mg GAE/g dry biomass, a yield of 27% and a selectivity of 75.2 mg GAE/g dry extract. Peleg’s model adequately described the kinetics at 20 and 60 °C; pseudo-equilibrium was reached within 5 min, with equilibrium concentration rising from 9.9 to 20.8 mg GAE/g DW, and initial rate tripling. Based on the kinetic analysis (t₉₉ ≈ 2.5 min), 5 min was adopted as the operational reference for phytochemical characterization; extracts were characterized by FRAP, DPPH, total anthocyanin content (TAC), and HPLC-DAD anthocyanin profiling. Increasing the temperature from 20 to 60 °C raised FRAP 3.4-fold and TAC 1.9-fold while reducing DPPH by 14%, decoupling bulk phenolic recovery from antioxidant capacity. HPLC-DAD identified five glycosylated anthocyanins, with petunidin-3-glucoside as the dominant constituent. Antimicrobial screening confirmed activity against Staphylococcus aureus. These results provide foundational process and compositional data to guide GRAS-compatible valorization of Chilean blueberry pomace and caution against bulk phenolic indicators as the sole quality criteria.