The occurrence of contact lens complications caused by inadequate cleaning of the lenses using “All-in-One” contact lens cleaning solutions (CLCSs) represents a medically relevant problem worldwide. This study explores the potential of cold atmospheric plasma (CAP) to enhance the efficacy of CLCSs and address complications from inadequate lens hygiene. It was examined whether exposure to CAP for 1–24 h could boost the antibacterial effects of CLCSs and other solutions, including Milli-Q water (M-QW), physiological saline (NaCl), and Dulbecco’s Phosphate Buffered Saline (DPBS). Additionally, the stability of reactive oxygen and nitrogen species (RONS) and their impact on pH immediately after treatment and over 1–4 weeks was assessed. Furthermore, the cleaning efficacy of plasma-activated solutions (PASs) was tested on lipid-coated silicone hydrogel lenses. Results showed that CAP increased RONS concentrations immediately, with elevated levels persisting over time. While no significant improved antibacterial effect was observed against Escherichia coli in CLCSs, CAP treatment generated disinfectant properties in M-QW and NaCl solutions. Importantly, CAP-treated CLCSs significantly improved the cleaning performance on lipid-coated lenses, though M-QW’s cleaning ability worsened post-treatment. pH measurements indicated notable decreases in M-QW and NaCl after CAP, whereas buffered solutions like CLCSs and DPBS remained stable. Overall, CAP demonstrates promise for contact lens disinfection and surface modification; however, further research and pre-clinical trials are necessary before clinical application in ophthalmology.