Background: Corneal refractive surgery induces high-order aberrations, specifically spherical aberration (SA). These aberrations can have implications when patients later develop cataracts and require the implantation of multifocal intraocular lenses (MIOLs). MIOLs with asymmetric designs pose challenges in predicting outcomes, particularly in these cases. The aim of this study was to evaluate how different values of SA, resulting from various types of refractive surgeries, affect the optical performance of the FEMTIS Comfort intraocular lens. Methods: The through-focus modulation transfer function (TF-MTF) curve and high-contrast images of tumbling E were used as parameters to assess the optical performance of the MIOL. These parameters were measured using an adaptive optics visual simulator. Results: Increasingly negative values of SA make the MIOL more bifocal, moderating its extended-depth-of-focus characteristic. Conversely, higher positive SA values cause the TF-MTF curve to shift towards positive vergences, leading to worsened distance vision in the +1.00 to +2.00 D range, but improved vision in the +0.50 D to +1.00 D range. Conclusions: Assessing SA in patients prior to implanting MIOLs with asymmetric designs is necessary for predicting outcomes and making informed decisions based on the visual requirements of patients.