Although biologics are highly effective in the treatment of psoriasis, some patients consistently fail monotherapy. For these patients, combination therapy is commonly employed. However, evidence-based recommendations for combination therapy in the treatment of psoriasis with interleukin-17 (IL-17) inhibitors are currently lacking. Therefore, we aimed to conduct a systematic review of existing literature discussing the efficacy and safety of IL-17 inhibitors in combination with other therapeutic modalities in the treatment of psoriasis.By way of a search of PubMed, Cochrane, and Web of Science databases in March 2021, we identified peer-reviewed articles with data on the safety and/or efficacy of IL-17 inhibitor combination therapies in adults with psoriasis and/or psoriatic arthritis (PsA). A modified version of the 2011 Oxford Centre for Evidence-Based Medicine Scheme was utilized for assessing study quality.Twenty-four articles with a total of 3,154 patients met inclusion/exclusion criteria. These articles comprised six post-hoc/subgroup analyses of randomized controlled trials (RCTs), four uncontrolled clinical trials, three case series, and 11 case reports that provided data on IL-17 inhibitor therapy in combination with conventional disease-modifying antirheumatic drugs (cDMARDs), apremilast, acitretin, topical therapy, phototherapy, and/or medications for comorbid diseases.Our results are limited by the lack of data from RCTs.Although cDMARDs are often used in psoriasis combination therapies, the current literature suggests concomitant cDMARDs with IL-17 inhibitor therapy provides no added benefit compared to IL-17 inhibitor monotherapy. However, IL-17 inhibitor in combination with apremilast or acitretin shows efficacy and safety in case series/reports and may allow for a reduction in medication dosing and/or frequency, thereby minimizing costs and adverse events. Future RCTs investigating IL-17 inhibitor therapy in combination with acitretin or apremilast are warranted.