Recent studies indicate that thermally produced dark matter will form highly concentrated, low-mass cusps in the early universe that often survive until the present. While these cusps contain a small fraction of the dark matter, their high density significantly increases the expected 𝛾-ray flux from dark matter annihilation, particularly in searches of large angular regions. We utilize 14 years of Fermi-LAT data to set strong constraints on dark matter annihilation through a detailed study of the isotropic 𝛾-ray background, excluding with 95% confidence dark matter annihilation to 𝑏⁢¯𝑏 final states for dark matter masses below 120 GeV.