We study single lepton production from semileptonic decays of heavy flavor hadrons (D, B → l) in pp and pA collisions at RHIC and the LHC within the saturation/Color-Glass-Condensate (CGC) framework. Using the gluon distribution function obtained with the dipole amplitude, whose energy dependence is described by the Balitsky-Kovchegov equation with running coupling effect, we compute the transverse-momentum (p ⊥ ) spectra of the lepton yields at mid and forward rapidities. We find that a large fraction of leptons at low p ⊥ stems from the saturation regime of the incoming gluons in the target, especially in pA collisions at the LHC. The resultant p ⊥ spectra is slightly harder than the data, but the nuclear modification factor seems consistent with the data within some uncertainty. We also update the nuclear modification factors for J/ψ and D meson at the LHC energy.