Improving nitrogen use efficiency (NUE) is essential for sustainable wheat production, given the global demand for high-yielding and environmentally resilient crop varieties. NUE is a complex trait governed by multiple genetic, physiological, and environmental factors. This review synthesizes recent advances in the genetic dissection of NUE in wheat, focusing on quantitative trait loci (QTL) mapping, genome-wide association studies (GWAS), and transcriptome analyses. Furthermore, novel approaches such as protein turnover quantification, epigenetic regulation, NIR-based quality prediction, and genomic selection optimization are discussed as emerging strategies to enhance NUE. Key genes identified include nitrate transporters (NRT1, NRT2), nitrogen assimilation enzymes (GS, GOGAT), transcription factors (NLPs, WRKYs, NACs), and signal transduction components (SnRK, CIPK). Integrative studies combining genomics, transcriptomics, and machine learning offer new insights into the dynamic regulation of NUE. This review highlights the importance of multi-layered breeding approaches and provides valuable genetic resources and methodological frameworks for future wheat NUE improvement programs.