Night shift work (NSW) has been known for its linkage with circadian disruption, while the NSW carcinogenic potential is well documented. However, there has been little research on the NSW-associated biological pathways and small molecules that may be implicated with the early stages of carcinogenicity. Metabolomics platforms are novel exposomics tools that act as intermediate biological layers of information linking NSW schedules with the downstream endogenous response in humans. To this extent, we conducted a scoping review to answer the question: how does NSW impact the endogenous human metabolome using metabolomics tools? Thus, this work critically reviewed human studies on the association between NSW and the associated endogenous biological response. Online databases were screened, and 13 original publications were included in the analysis; eight studies were conducted in occupational settings, and the remaining studies were well-controlled laboratory experiments simulating NSW. This work summarized the consistent reporting of the most frequently reported metabolites and associated biological pathways enriched in actual NSW, or in simulated NSW conditions of occupational and experimental laboratory studies, respectively. Further research is warranted to better understand the complex metabolic changes associated with NSW, informing strategies to mitigate early-stage carcinogenic effects, ultimately improving health and well-being of shift workers.