Mendelian randomization (MR) studies show that higher body mass index (BMI) and lower 25-hydroxyvitamin D (25[OH]D) increase psoriasis risk. The combined effect of these factors has not been explored using factorial MR. Using cross-sectional data from UK Biobank (n = 398,404) and The Trøndelag Health Study (n = 86,648), we calculated polygenic risk scores for BMI and 25(OH)D to estimate ORs for psoriasis using 2 × 2 and continuous factorial MR. We quantified additive interaction by estimating relative excess risk due to interaction. We also performed traditional observational analyses in UK Biobank. There were 12,207 (3.1%) participants with psoriasis in UK Biobank and 7794 (9.0%) in The Trøndelag Health Study. In 2 × 2 factorial MR, we found no evidence of relative excess risk for psoriasis due to interaction between genetically predicted higher BMI and lower 25(OH)D, neither in UK Biobank (relative excess risk due to interaction = -0.01, 95% confidence interval = -0.08 to 0.07) nor in The Trøndelag Health Study (relative excess risk due to interaction = -0.04, 95% confidence interval = -0.14 to 0.06). The same was observed in the continuous factorial MR and observational analyses. In conclusion, this study did not find evidence of interaction between BMI and 25(OH)D on the risk of psoriasis. Given minor differences in measured BMI and 25(OH)D between the factorial groups, small effects may have been undetected.