Background: It is unknown whether the pre-biologic treatment journey affects subsequent biologic drug survival. Objective: To examine the potential impact of a complex treatment journey on subsequent biologic drug survival in patients with psoriasis. Methods: The study utilized longitudinal data from Danish national registries and included all patients who, for the first time, initiated a biological treatment for psoriasis. Maximum follow-up was 5 years and patients were included from 1 January 2010 to 30 June 2021. The study used three definitions of exposure to a complex treatment journey and the following conventional systemic treatments: acitretin, cyclosporine, dimethyl fumarate and methotrexate. The first definition was the cumulative number of treatment series. The second definition comprised the number of unique treatments. The third definition was time from the first conventional systemic treatment to biological therapy. Drug survival for the three definitions were illustrated using Kaplan–Meier curves and compared using log-rank test. The sensitivity analysis largely confirmed these findings by grouping patients according to pharmacotherapy. Results: A total of 2496 patients were included in the study, with 1380 (55.3%) receiving adalimumab, 608 (24.4%) receiving ustekinumab, 271 (10.9%) receiving secukinumab, 166 (6.7%) receiving etanercept and 71 (2.8%) receiving infliximab. The mean age at initiation of biologics was 43.6 years (standard deviation (SD) 15.2 years), and most patients were male (62.9%). During the follow-up of 5477 patient years, 1953 patients (78.2%) reached the main endpoint of discontinuation. Using a log-rank test, the probability of remaining on treatment was unaffected by the three definitions of complexity of the treatment journey. Conclusion: None of the three exposures used to assess the complexity of the pre-biologic treatment journey appeared to impact drug survival. As long as patients experience adequate disease control, these results suggest that conventional systemic treatment do not negatively impact the drug survival of subsequent biologics.