Short-distance new physics at (or slightly) above the TeV scale should not excessively violate the approximate flavor symmetries of the SM in order to comply with stringent constraints from flavor-changing neutral currents. In this respect, flavor symmetries provide an effective organizing principle for the vast parameter space of the SMEFT. In this work, we classify all possible irreducible representations under U(3)5 flavor symmetry of new heavy spin-0, 1/2, and 1 fields which integrate out to dimension-6 operators at the tree level. For a general perturbative UV model, the resulting flavor-symmetric interactions are very restrictive and, in most cases, predict a single Hermitian operator with a definite sign. These leading directions in the SMEFT space deserve particular attention. We derive an extensive set of present experimental constraints by utilizing the existing global SMEFT fits, which incorporate data from top quark, Higgs boson, and electroweak measurements, along with constraints on dilepton and 4-lepton contact interactions. The derived set of bounds comprehensively summarises the present knowledge from indirect searches of flavor-blind new physics mediators.