Summary: Myo‐inositol‐1‐phosphate synthase (MIPS) is a key rate limiting enzyme inmyo‐inositol biosynthesis. TheMIPSgene has been shown to improve tolerance to abiotic stresses in several plant species. However, its role in resistance to biotic stresses has not been reported. In this study, we found that expression of the sweet potatoIbMIPS1gene was induced by NaCl, polyethylene glycol (PEG), abscisic acid (ABA) and stem nematodes. Its overexpression significantly enhanced stem nematode resistance as well as salt and drought tolerance in transgenic sweet potato under field conditions. Transcriptome and real‐time quantitativePCRanalyses showed that overexpression ofIbMIPS1up‐regulated the genes involved in inositol biosynthesis, phosphatidylinositol (PI) andABAsignalling pathways, stress responses, photosynthesis andROS‐scavenging system under salt, drought and stem nematode stresses. Inositol, inositol‐1,4,5‐trisphosphate (IP3), phosphatidic acid (PA), Ca2+,ABA, K+, proline and trehalose content was significantly increased, whereas malonaldehyde (MDA), Na+and H2O2content was significantly decreased in the transgenic plants under salt and drought stresses. After stem nematode infection, the significant increase of inositol,IP3,PA, Ca2+,ABA, callose and lignin content and significant reduction ofMDAcontent were found, and a rapid increase of H2O2levels was observed, peaked at 1 to 2 days and thereafter declined in the transgenic plants. This study indicates that theIbMIPS1gene has the potential to be used to improve the resistance to biotic and abiotic stresses in plants.