We adopted an omics (transcriptome, proteome, and metabolome) approach to characterize the lens fiber cells extracted from control (CT) and cigarette smoke (CS) exposed mouse (C57BL/6) eyes. The eight pregnant female mice (gestation days 19-20) were placed in a whole-body exposure smoking chamber and served as a CS-exposed group. The mothers and newborn pups were exposed to CS for five hours/day, five days/week for 110 days. In parallel, age-matched mice were kept in normal cages and served as a control group. The ophthalmic examination revealed no sign of cataracts in CS-exposed and aged-matched CT mice. The ocular lenses were extracted and fiber cells (FC) were separated from the lens epithelium under a microscope. The CT and CS fiber cells were maintained in four biological replicates each consisting of a pool of lens fiber cells from four eyes. The eight biological replicates including four CT and four CS-exposed fiber cells were used for the next-generation-based transcriptome (RNA-Seq), mass-spectrometry-based proteome, and metabolome profiling. RNA-Seq analysis identified the expression (≥1.0 FPKM) of 9,590 and 9,531 genes in CT and CS-exposed fiber cells, respectively. The analysis identified 348 differentially expressed genes, including 186 downregulated and 162 upregulated genes in CS-exposed fiber cells. Proteome profiling revealed a total of 2,424 proteins in CT and CS exposed fiber cells. The analysis identified 42 downregulated and 59 upregulated proteins in CS exposed fiber cells. Metabolome profiling identified a total of 280 metabolites, marked with decreased levels of branched-chain amino acids (BCAAs)-related metabolites in CS exposed fiber cells. In conclusion, we have established a comprehensive omics profile of fiber cells from CS-exposed mice. To the best of our knowledge, this is the first report investigating a comprehensive omics profile of fiber cells from CS-exposed mice.