A printed circuit heat exchanger (PCHE) with zigzag flow channels in a double-faced configuration was optimized to enhance its thermal–hydraulic performance. Using exergy analysis, the objective function was defined as the net exergy gain of the system considering the exergy gain by heat transfer and exergy loss due to friction in the channels. A Reynolds-averaged Navier–Stokes (RANS) analysis and surrogate modeling techniques were used for the optimization. Three geometric variables were selected as the design variables. The objective function was calculated at each design point through RANS analysis in order to construct a response surface surrogate model. Through the optimization, both the thermal and hydraulic performances of the PCHE were improved with respect to the reference geometry by suppressing flow separation in the channels.