To overcome the problem of difficult separation of the 1,3-dioxane (DOL)-H2O azeotrope in the production of DOL, a new high-integrated technology via reactive distillation (RD) with inter-integrated vapor permeation (VP) (abbreived as R-VP-D) was established. A series of R-VP-D experiments were conducted to find the effect of dedydration on reactant conversion and DOL content in the distillate. A two-dimensional VP module modeled by Aspen Custom Modeler (ACM) was combined with two RD modules in Aspen Plus to simulate the entire R-VP-D process, and the R-VP-D model was verified by experimental results. Then, by this model, systematic research on VP inserting position and membrane area on the reaction performance, reboiler and condenser duty, catalyst load, and TAC of the R-VP-D column was performed. The mechanism of how dehydration promotes reaction was explored. Finally, a new RD-VP-D technology for producing 99.9wt% DOL was designed and optimized. Two goals were achieved by inserting VP: obtaining a DOL-H2O mixture that crosses the azeotropic point in the distillate and improving reaction performance by removing by-product H2O. Under the optimal parameter, the energy consumption per unit product was reduced by 3.9% with less equipment, a simpler process, and less required land area compared with the RD with pressure swing distillation technology reported in the literature, and CO2 emissions were reduced by 4.0%. The reason why promotion effect is insignificant was explored, which is related to which of separation or reaction is the control step in RD process.