Compared with the traditional solvothermal approach that synthesizes MOFs on a small scale while demanding high temperature, high pressure, and large amounts of toxic organic solvents, in this Account, we elaborate on the recent progress of the modulated hydrothermal (MHT) chemistry developed by us, which helps synthesize MOFs in a green (aqueous solutions), mild (≤ 120 °C, 1 atm), and scalable (~ 100 kg m^-3 day^-1) fashion. The MHT approach has already served as a solid foundation for the kinetic design and scale-up production of multifunctional MOF materials by tuning the types and concentrations of modulators and the ratios of ligands to modulators. It not only applies to the classical UiO-66-type and MOF-808-type MOFs but also suits the design of new MOFs, such as NUS-6, NUS-8, and NUS-36. In addition, the MHT-enabled MOFs have demonstrated promising applications in robust gas separation and storage, Lewis/Brønsted acid-catalyzed oxidation reactions/biomass conversion, and as piezo-/ferro-electric devices.