This study investigates proteomic changes in two human cancer cell lines—A375 (melanoma) and OVCAR3 (ovarian cancer)—after infection with either Staphylococcus aureus (USA300 wildtype or ΔfnbAB mutant) or Salmonella enterica (SL1344). Using label-free quantitative proteomics, we observed that bacterial infections induced widespread remodeling of the host proteome, with mitochondrial and stress-related proteins generally upregulated, and proteins involved in DNA repair, cytoskeletal structure, and vesicle trafficking downregulated. The study highlights how bacterial invasion influences cancer cell responses.