Propylene glycol monomethyl ether acetate (PGMEA) photoresist solvent and monoaromatics are typical organic pollutants found in the wastewater discharged from semiconductor manufacturing processes. Conventional treatment technologies, however, remain mostly ineffective to eliminate these pollutants from aqueous streams. Herein, we developed a novel strategy for highly efficient degradation of PGMEA and archetypal monoaromatics (i.e., benzene, toluene, xylene, phenol, and cresol) in aqueous solution by heterogeneous Fenton-like process with a flexible Fe-MOF (MIL-88B) under mild subcritical water (SCW) condition (100 °C). The as-synthesized MIL-88B(Fe) microbipyramids possess large pore channels (∼32 nm) and open iron sites. The results showed that the SCW-mediated heterogeneous Fenton-like process at 100 °C with an optimal catalyst loading of 1 wt% exhibited a remarkable degradation performance toward target organic pollutants in a multicomponent system, affording a 92% total organic carbon (TOC) removal in 60 min. This mineralization efficiency was found to be notably superior to those of traditional homogeneous Fenton (FeSO4/H2O2; ∼54%) and Fenton-SCW (∼60%) processes. The practicability of this approach was demonstrated using real world water samples (i.e., river water, fishpond water, and wastewater) with >80% TOC removal efficiency. This study showed that the heterogeneous Fenton-like process utilizing an inexpensive, nontoxic, and reusable MIL-88B(Fe) MOF under mild SCW conditions is a promising strategy for treating semiconductor waste effluents and environmental water matrices containing toxic recalcitrant organics in an eco-friendly and efficient manner.