PurposePersonalized synthetic MRI (syn‐MRI) uses MR images of an individual subject acquired at a few design parameters (echo time, repetition time, flip angle) to obtain underlying parametric maps, from where MR images of that individual at other design parameter settings are synthesized. However, classical methods that use least‐squares (LS) or maximum likelihood estimators (MLE) are unsatisfactory at higher noise levels because the underlying inverse problem is ill‐posed. This article provides a pipeline to enhance the synthesis of such images in three‐dimensional (3D) using a deep learning (DL) neural network architecture for spatial regularization in a personalized setting where having more than a few training images is impractical.MethodsOur DL enhancements employ a Deep Image Prior (DIP) with a U‐net type denoising architecture that includes situations with minimal training data, such as personalized syn‐MRI. We provide a general workflow for syn‐MRI from three or more training images. Our workflow, called DIPsyn‐MRI, uses DIP to enhance training images, then obtains parametric images using LS or MLE before synthesizing images at desired design parameter settings. DIPsyn‐MRI is implemented in our publicly available Python package DeepSynMRI available at: https://github.com/StatPal/DeepSynMRI.ResultsWe demonstrate feasibility and improved performance of DIPsyn‐MRI on 3D datasets acquired using the Brainweb interface for spin‐echo and FLASH imaging sequences, at different noise levels. Our DL enhancements improve syn‐MRI in the presence of different intensity nonuniformity levels of the magnetic field, for all but very low noise levels.ConclusionThis article provides recipes and software to realistically facilitate DL‐enhanced personalized syn‐MRI.