This chapter summarizes the technical components that determine image quality and quantitative performance in hybrid imaging systems used in nuclear medicine. Image quality is evaluated using measurable metrics such as lesion detectability, contrast, noise, and spatial resolution, and a target-metric definition approach is adopted according to the clinical objective. Hardware-related components include detector technology and geometry, collimator characteristics, field of view, and count-rate limitations. At the acquisition stage, the balance between administered activity and acquisition time, acquisition time per bed position, matrix size and pixel/voxel dimensions, sampling angle, energy window selection, respiratory and patient motion management, and the effect of patient-related factors on the noise–contrast trade-off are described. For the computed tomography component, tube voltage and tube current selection, metal artifacts, and the accuracy of the computed tomography–based photon attenuation map are addressed; for magnetic resonance imaging, segmentation errors, coil/implant attenuation, and timing mismatch in magnetic resonance–based photon attenuation correction are discussed. Within the reconstruction and correction chain, the effects of photon attenuation and scatter correction, dead-time correction, point spread function and time-of-flight modeling, iteration–subset selection, post-filtering, and partial volume effects on both image appearance and standardized uptake value and activity measurements are summarized. Finally, cross-calibration, phantom-based validation, standardized parameter reporting, and a continuous quality control/quality assurance framework are emphasized for inter-center comparability; optimization is recommended to be performed using measurable targets tailored to the defined clinical question rather than a single universal protocol.