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Heavy metal-induced oxidative stress and its connection with different signaling pathways are complicated; therefore, the systemic summary is essential. Herein, an effort has been made to decipher the interplay among heavy metals/metalloids (Arsenic, Chromium, Cadmium, and Lead) exposures, oxidative stress, and signal transduction, which are essential to mount the cellular and organismal response. The signaling pathways involved in this interplay include NF-κB, NRF2, JAK-STAT, JNK, FOXO, and HIF.Owing to the superlative properties, engin