Cerro Quema (Azuero Peninsula, southwest Panama) is a high-sulfidation epithermal Au-Cu deposit hosted by a dacite dome complex of the Río Quema Formation (late Campanian to Maastrichtian), a fore-arc basin sequence. Mineral resource estimates (indicated + inferred) are 30.86 Mt at 0.73 g/t Au, containing 728,000 oz Au (including 76.900 oz Au equiv of Cu ore). Hydrothermal alteration and mineralization are controlled by an E-trending regional fault system. Hydrothermal alteration consists of an inner zone of vuggy quartz with locally developed advanced argillic alteration, enclosed by a well-developed zone of argillic alteration, grading to an external halo of propylitic alteration. Mineralization produced disseminations and microveinlets of pyrite and minor chalcopyrite, enargite, and tennantite, with traces of sphalerite, crosscut by late-stage base metal veins. New 40Ar/39Ar data of igneous rocks combined with biostratigraphic ages of the volcanic sequence indicate a maximum age of lower Eocene (~55–49 Ma) for the Cerro Quema deposit. It was probably triggered by the emplacement of an underlying porphyry-like intrusion associated with the Valle Rico batholith. The geologic model suggests that in the Azuero Peninsula high-sulfidation epithermal mineralization occurs in the Cretaceous-Paleogene fore arc. This consideration should be taken into account when exploring for this deposit type in similar geologic terranes.