Background: This meta-analysis was conducted aiming at assessing the risk of selected dermatological toxicities associated with MEK inhibitors. Methods: We considered relevant prospective randomized Phase II and III trials of cancer patients on the three MEK inhibitors (trametinib, selumetinib and cobimetinib), describing events of skin rash and acneiform dermatitis, as eligible for inclusion. Results: After exclusion of ineligible studies, a total of 14 clinical trials were considered eligible for the meta-analysis. The relative risk of all-grade skin rash and acneiform dermatitis was 1.71 (95% CI: 1.07–2.72; p = 0.02) and 6.55 (95% CI: 3.42–12.56; p < 0.00001), correspondingly; while the relative risk of high-grade skin rash and acneiform dermatitis was 2.64 (95% CI: 1.42–4.91; p = 0.002) and 8.44 (95% CI: 2.39–29.81; p = 0.0009), respectively. Conclusion: Our meta-analysis has demonstrated that MEK inhibitor-based treatment is associated with an increased risk of all-grade and high-grade skin rash and acneiform dermatitis compared with control.