The reactions of formaldehyde oxide (CH2OO) with methane and ethane that yield alcohol products were investigated using dual-level variational transition state theory with multidimensional tunneling corrections (VTST/MT). Additional systems—including halogenated formaldehyde oxides (CF2OO and CCl2OO), deuterated alkanes (CD4, C2D6), and isotopically substituted formaldehyde oxide (CH2 18O18O)—were also examined to explore substituent and isotope effects. Bimolecular rate constants and kinetic isotope effects (KIEs) were computed over the temperature range of 100–600 K. Significant tunneling contributions were predicted, especially below room temperature, where tunneling increases the rate constants of the CH2OO + alkane reactions by up to two orders of magnitude. The computed H/D KIEs are approximately 3 at 300 K and rise to ~10 at 200 K. Notably, pronounced oxygen tunneling was also observed, giving 18O KIEs of ~1.2 at 300 K and ~2.2 at 200 K. Halogen substitution was predicted to substantially reduce reaction barriers due to the weakening of the O–O bond, leading to rate constants for CF2OO reactions that exceed those of CH2OO by more than ten orders of magnitude at 300 K. The mechanisms underlying the strong tunneling effects, the individual contributions to the calculated KIEs, and the implications of these findings for atmospheric chemistry are discussed.