Methods and systems for calibrating a nuclear medicine imaging system are provided. One method includes acquiring spatially determined non-uniform radiation flux information from a calibration scan of a calibration source using a gamma camera having an attached non-parallel-hole collimator. The method further includes determining a measured non-uniform count density profile from the acquired non-uniform radiation flux information. The method also includes creating a gamma camera uniformity correction map derived from (i) the measured non-uniform count density profile and (ii) a modeled or calculated non-uniform count density profile for calibrating the NM imaging system.