Metal ions are essential for cellular function, serving roles in enzymatic catalysis, signaling, and structural stability. While endogenous metals such as zinc are tightly regulated, exposure to exogenous metals from environmental sources can disrupt cellular homeostasis. Electronic nicotine delivery systems (ENDS) have emerged as a significant source of metal exposure, with toxic metals (e.g., Pb, Ni, Cr, Cu) detected in commercial e-liquids. To assess the aerosolization of these metals, we developed a controlled ENDS aerosolization system and demonstrated that metal content in aerosols varies based on e-liquid composition. These findings provide a foundation for evaluating the health risks of metal exposure from ENDS. Zinc, an essential trace metal, plays a crucial role in the structure and function of zinc finger proteins (ZFs), which are susceptible to post-translational modifications such as persulfidation (RSH → RSSH) by hydrogen sulfide (H₂S). We identified persulfidation as a widespread regulatory modification in ZFs using a meta-analysis of persulfide-specific proteomics data. Many persulfidated ZFs were enriched in the NF-κB signaling pathway, a key regulator of inflammation. Using THP-1 monocytes, we demonstrated that inflammatory stress increases global persulfidation, with ZFs being prominent targets. A20, a critical NF-κB repressor, was identified as persulfidated, and mechanistic studies with ZF peptides confirmed persulfidation mechanism is the same as other type of ZFs which requires H2S and oxygen. These findings highlight the dual impact of metals on cellular systems, from exogenous metal toxicity in ENDS to the regulatory role of endogenous zinc in ZFs.