Powerful blazars are flat-spectrum radio quasars whose emission is dominated by a Compton component peakingbetween a few hundred keV and a few hundred MeV. We observed two bright blazars, PKS 2149–306 at redshift z = 2.345 and S5 0836+710 at z = 2.172, in the hard X-ray band with the Nuclear Spectroscopic Telescope Array satellite. Simultaneous soft-X-rays and UV–optical observations were performed with the Swift satellite, whilenear-infrared (near-IR) data were obtained with the Rapid Eye Mount telescope. To study their variability, we repeated these observations for both sources on a timescale of a few months. While no fast variability was detected during a single observation, both sources were variable in the X-ray band, up to 50%, between the two observations, with larger variability at higher energies. No variability was detected in the optical/NIR band. These data, together with Fermi-Large Area Telescope, Wide-field Infrared Survey Explorer, and other literature data, are then used to study the overall spectral energy distributions (SEDs) of these blazars. Although the jet nonthermal emission dominates the SED, it leaves the UV band unhidden, allowing us to detect the thermal emission of the disk and to estimate the black hole mass. The nonthermal emission is well reproduced by a one-zone leptonic model by the synchrotron, self-Compton, and external Compton processes. Our data are better reproduced if we assume that the location of the dissipation region of the jet, Rdiss, is in between the torus and the broad-line region.The observed variability is explained by changing a minimum number of model parameters by a very smallamount.