Background/Objectives: The management of moderate-to-severe psoriasis in patients with a recent history of internal malignancy is a clinical challenge, as systemic immunosuppressive therapies are often avoided because of concerns about cancer recurrence. While Psoralen and Ultraviolet A (PUVA) photochemotherapy remains a valuable non-immunosuppressive alternative, regional variations in therapeutic response are not well-characterized in this population. This study aimed to evaluate total and segmental Psoriasis Area and Severity Index (PASI) responses to PUVA in patients with chronic plaque psoriasis and recent internal organ malignancy. Methods: This prospective, single-center, real-world cohort study enrolled 20 adults with moderate-to-severe chronic plaque psoriasis and a recent (<5 years) diagnosis of internal organ malignancy in complete remission. Participants received oral PUVA three times weekly for up to 30 sessions. Primary and secondary outcomes included changes in total PASI, segmental PASI (head/neck, trunk, upper limbs, and lower limbs), and Dermatology Life Quality Index (DLQI) at baseline, completion of therapy, and 6 months post-treatment. Results: PUVA led to a significant reduction in mean total PASI from 18.6 ± 3.2 at baseline to 5.7 ± 6.0 at treatment completion (69% reduction; p < 0.001). However, regional responses differed significantly: the head and neck improved the most (80.4%), followed by the trunk (72.2%) and upper limbs (72.3%), while the lower limbs showed the weakest response (59.5%; p < 0.001). At baseline, trunk contributed the most to total PASI (38%), while post-treatment, lower-limb lesions accounted for approximately 47% of the remaining total disease burden, showing the highest contribution to total PASI of all body regions. At 6 months, the lower limbs remained the most affected area, with significantly lower improvement (52.9%) compared to other regions. Mean DLQI also improved significantly from 17.2 ± 2.8 to 5.6 ± 2.6 (p < 0.001). Conclusions: PUVA is an effective and safe treatment for patients with psoriasis and a recent history of malignancy. Nevertheless, lower-limb psoriasis is relatively recalcitrant and contributes disproportionately to residual disease burden and relapse. These findings support the use of regional PASI assessment to guide individualized management and clinical expectations in this complex patient group.