The regional SSI mapping enabled the spatial material description of keratoconus-induced softening in place of its previous representation as a global biomechanical variable. In this context, the present investigation poses the question: could the spatial nature of regional SSI deficits be exploited to design customized keratoconus CXL? For that purpose, the study adopted a computational method to translate a presurgical SSI deficit map of keratoconus into a stiffness-deficit map, represented as Gaussian sector-based fields of anisotropic treatment, and evaluated by simulation under optical, biomechanical, and geometrical constraints. A group of 48 hypothetical eyes was modeled using combinations of four cone radii, three cone decentration values, two orientations, and two keratoconus severities. The proposed map-optimized CXL (MO-CXL) method was compared to centered circle-based CXL (CCXL), decentered circle-based CXL (DCXL), and symmetrical bow-tie CXL (BCXL). Map optimization led to designs with minimal residual cone stiffness deficit (9.7 ± 3.7%), peak cone strain (5.9 ± 1.3%), root-mean-square curvature disturbance (0.86 ± 0.31 D), and total treated area (20.7 ± 2.8 mm2) while fully maintaining safety requirements. With regard to the baseline CCXL strategy, MO-CXL reduced the deficit, strain, curvature, and treated area by 54.7%, 32.2%, 53.3%, and 58.8%, respectively. The results thus answered positively the research question raised at the outset: yes, regional SSI maps can be effectively utilized as design targets in computationally tailored CXL plans.