Metal (loid) contamination in food poses a significant global health concern and represents a long-term threat to crop growth and agricultural sustainability. This study focused on the Henan Province of China (Yuzhou and Jiyuan) and the Marche region of Italy (Jesi and Camerino) to analyze the uptake and translocation characteristics of heavy metals (HMs) in wheat across different regions. Additionally, it employed chemometric and transcriptomic techniques to compare the effects of organic (Org) and conventional (Conv) cultivation. Results showed significant regional differences in soil pollution profiles: Pb and Cd dominated in Jiyuan, Cd in Yuzhou, and Al and Cu in Jesi. The bioaccumulation factors (BAF) of Cr, Ni, and As in wheat grains were significantly higher in the two locations in Henan compared to those in Marche, indicating a greater propensity for these metals to be translocated and accumulated in the grains. During the tillering stage, wheat actively absorbed and translocated Mn, Al, and Cd, whereas Pb, As and Ni accumulated predominantly during the filling stage, demonstrating stage-specific responses of wheat to HM stress. Org reduced soil HM contents by an average of 1.29 % annually compared to Conv. Wheat grown near railways (Org-rial) exhibited an average increase of 21.25 % in HM contents, indicating a stimulatory effect of railway pollution on HM uptake and accumulation. Transcriptomic analysis identified 25,102 differentially expressed genes in wheat leaves under Org. Org significantly enhanced the expression of genes involved in metabolic pathways, photosynthesis, and antioxidant mechanisms, while suppressing the expression of certain HM transport-related genes. This study underscores the potential of Org to mitigate HM accumulation in crops, contributing to enhanced food safety and sustainable agricultural practices.