Identifying and quantifying genotoxic impurities (GTIs) in drug substances at trace levels is a difficult task that necessitates using sophisticated, hyphenated analytical techniques. This study provides a complete overview of the current analytical methodologies used for the detection and measurement of GTIs in pharmacological compounds. It focuses on risk assessment and the many analytical approaches used by regulatory agencies and researchers. This review outlines the numerous sources of GTIs while also digging into the industrial processes that lead to their development. A comprehensive range of analytical techniques, including both chromatographic and non-chromatographic approaches, is thoroughly described. Popular analytical techniques such as high-performance liquid chromatography (HPLC), gas chromatography (GC), mass spectrometry single quad LCMS, GCMS, and triple quad approaches have distinct applications, strengths, and limitations. Capillary electrophoresis (CE), LC-MS/MS, GC-MS/MS, LC-HRMS/MS, and Microbial reverse mutation assay (Ames)s for analyzing genotoxic impurities, as well as other hyphenated techniques, were discussed. In addition, The review addresses the issues encountered in GTI analysis, including setting acceptance criteria, defining appropriate reference standards, and validating analytical methodologies. Regulatory rules and requirements established by governing organizations are also investigated. Furthermore, emerging trends and breakthroughs in the field, such as in-silico prediction tools, novel sample preparation processes, and rapid screening approaches, are highlighted. The use of quality-by-design (QbD) principles and automated technologies to improve efficiency is also highlighted. This evaluation is a significant resource for researchers, regulatory bodies, and pharmaceutical companies.