<b><i>Background:</i></b> Interleukin (IL) inhibitors have made <i>completely cleared skin</i> achievable for many patients with moderate to severe psoriasis in clinical trial settings. Few observational studies assess treatment response in accordance with treatment goals in guidelines. <b><i>Objectives:</i></b> The aim of the study was to analyze the treatment response of IL-17/IL-23 inhibitors in clinical practice and the proportions of patients that reach the treatment target of the Psoriasis Area and Severity Index (PASI) < 3 and the Dermatology Life Quality Index (DLQI) ≤5. <b><i>Methods:</i></b> A longitudinal, observational study based on the Swedish National Registry for Systemic Treatment of Psoriasis, PsoReg. Patients using IL-17/IL-23 inhibitors with assessments of PASI, DLQI, and EQ-5D before (maximum 6 months) and after (3–12 months) initiation of IL-17/IL-23 were included. <b><i>Results:</i></b> In total, 333 patients using IL-17/IL-23 inhibitors were included. Eighty percent (<i>n</i> = 266) received IL-17 inhibitors, and 20% (<i>n</i> = 67) received IL-23 inhibitors. Sixty-six percent of patients reached both PASI <3 and DLQI ≤5, 23% reached one target, and 11% reached none. The mean (SD) PASI, DLQI, and EQ-5D improvements were 6.75 (6.99), 7.14 (7.97), and 0.126 (0.296), respectively. There was no statistically significant difference in outcomes between IL-17 and IL-23 inhibitor treatment groups. <b><i>Conclusions:</i></b> IL-17/IL-23 inhibitors are effective in clinical practice, but there is still an unmet therapeutic need in moderate to severe psoriasis.