<p>Mucoepidermoid carcinoma (MEC) is the most common malignancy of the salivary glands. Its management typically depends on the tumor’s stage, grade, and molecular characteristics. Due to the heterogeneous nature of MEC, there is no standardized systemic therapy, which is generally reserved for cases of recurrence or metastasis. This paper aims to systematically review and summarize the available evidence on systemic treatments for MEC and to outline potential therapeutic options. Studies involving patients with recurrent, metastatic, or advanced MEC involving major or minor salivary glands who received systemic therapy were included in the review. Given the heterogeneity of the disease, no limitations were imposed on the study design. A total of 148 records were identified through the search, with 32 articles meeting the criteria for full-text inclusion. Most of the included studies were phase 2 clinical trials. Findings suggest that while conventional chemotherapy has shown limited effectiveness, targeted therapies—particularly HER2-directed treatments—have demonstrated some promising objective responses. Additionally, taxane-based regimens have shown potential benefit in a few small case series and early-phase trials. HER2-targeted therapies and taxane-based regimens have shown encouraging responses in some patients. Among chemotherapy options, cisplatin-based treatments have yielded variable outcomes, though combinations with taxanes appear to enhance efficacy. Evidence for other targeted therapies and immunotherapies remains anecdotal, making it difficult to establish clear treatment recommendations for these agents.</p>