To provide a relationship between materials developed for silicone hydrogel contact lenses and multipurpose care solutions to identify improvements in wettability, for prelens noninvasive break-up time and subjective score. This systematic review was completed according to the updated PRISMA 2020 statement recommendations and followed the explanation and elaboration guidelines. The PubMed, Web of Science, and Scopus scientific literature databases were searched from January 2000 to November 2021. A total of four clinical trials published between 2011 and 2017 were included in this investigation. All included studies were randomized clinical trials. The success of contact lenses is related to the comfort of their use and therefore to the stability of the tear film and the wettability of its surface. The relationship between these parameters and changes in the ocular surface and inflammatory and infectious processes has been demonstrated. Hyaluronan and propylene glycol multipurpose solution (MPS) wetting agents achieved slightly higher prelens noninvasive break-up times than poloxamine. Polyquaternium-1 achieved better wettability and patient comfort than polyhexamethylene biguanide in medium-term studies. Short-term studies did not demonstrate differences between MPSs in their effect on contact lens wettability.