Methods and systems for combining information present in measured images of semiconductor wafers with additional measurements of particular structures within the measured images are presented herein. In one aspect, an image-based signal response metrology (SRM) model is trained based on measured images and corresponding reference measurements of particular structures within each image. The trained, image-based SRM model is then used to calculate values of one or more parameters of interest directly from measured image data collected from other wafers. In another aspect, a measurement signal synthesis model is trained based on measured images and corresponding measurement signals generated by measurements of particular structures within each image by a non-imaging measurement technique. Images collected from other wafers are transformed into synthetic measurement signals associated with the non-imaging measurement technique and a model-based measurement is employed to estimate values of parameters of interest based on the synthetic signals.