Selenium (Se) and zinc (Zn) deficiencies have become serious global food security and public health problems. Biofortification through foliar fertilizer is a nonspecific, low-tech, and cost-effective strategy. Se and Zn have overlapping physiological roles and interacting relationships in plants. Mung bean is superior for Se enrichment and an excellent Zn carrier. However, the molecular mechanism underlying the interaction between Se and Zn in the mung bean remains unclear. Herein, Se and Zn accumulation, antioxidant activities, physiological determination, and transcriptomic analysis were performed under both Se and Zn treatments. Common essential roles of Se and Zn in mung bean were reflected by the comprehensively altered ten physiological indexes under both Se2 (24 g·ha-1) and Zn1 (1.2 kg·ha-1) treatments. Overlapping transcriptome changes and common DEGs in two compared groups revealed that the upregulated expression of sulfate transporters (SULTRs), phosphate transporters (PHTs), and Zinc-regulated/Iron-regulated-like protein (ZIP) family genes under Se and Zn treatments directly promoted both Se and Zn intakes. Furthermore, the altered Se/Sulfur, nitrogen, and carbohydrate metabolisms are closely interlinked with the uptake and assimilation of Se and Zn via the 20 key genes that we filtered through the protein-protein interaction (PPI) network analysis. Further analysis indicated that l-methionine γ-lyase (E 4.4.1.11) genes may play an important role in the transamination of selenomethionine and its derivatives; glutamine synthetase (GS), nitrate reductase (NR), and starch synthase (SS) genes may regulate the nitrogen assimilation and carbohydrate metabolism, which provide more carriers for Se and Zn; glutathione peroxidase (GPx), glutamate-cysteine ligase catalytic subunit (GCLC), and serine acetyltransferase (SAT) genes may accelerate the GSH-GSSH cycle and promote Se and Zn storages. This study provides new molecular insights into the comprehensive improvement of the nutritional quality of mung beans in Se and Zn biofortification productions.