An unusually large thermopower (S) enhancement is induced by heterostructuring thin films of the strongly correlated electron oxide LaNiO3. The phonon-drag effect, which is not observed in bulk LaNiO3, enhances S for thin films compressively strained by LaAlO3 substrates. By a reduction in the layer thickness down to three unit cells and subsequent LaAlO3 surface termination, a 10 times S enhancement over the bulk value is observed due to large phonon drag S (Sg), and the Sg contribution to the total S occurs over a much wider temperature range up to 220 K. The Sg enhancement originates from the coupling of lattice vibration to the d electrons with large effective mass in the compressively strained ultrathin LaNiO3, and the electron-phonon interaction is largely enhanced by the phonon leakage from the LaAlO3 substrate and the capping layer. The transition-metal oxide heterostructures emerge as a new playground to manipulate electronic and phononic properties in the quest for high-performance thermoelectrics.