The one-step methanol oxidation to dimethoxymethane (DMM) is a promising method for value-added chemical synthesis. However, vanadium cerium (VCe) catalysts commonly exhibit insufficient DMM selectivity in spite of its moderate high-temperature methanol conversion. In this work, titanium dioxide (TiO2) with relatively strong acidity was introduced into VCe catalyst to improve the catalysis performance of VCe. The results showed that the addition of TiO2 enhanced the oxidation reduction and surface acidity of the catalyst, and effectively improved the selectivity and yield of DMM. Furthermore, a scaled-up conceptual process for the one-step oxidation of methanol to DMM was explored, designed and economically evaluated based on the TiO2 modified catalysts. The entire conceptual process featured that multiple condensation-separation/absorption units offered a complete collection of the DMM. Through the optimization of the process, the generated products and unreacted methanol can be directly stripped from N2 and O2, and complete separation of DMM-methanol azeotrope was achieved with only one vacuum distillation unit. The entire process at what catalysis performance (methanol conversion, DMM selectivity, etc.) could bring profit was revealed and discussed. This study emphasizes the interaction between catalyst design, conceptual process design and economic evaluation, providing new ideas for the development of efficient industrial catalysts.