High-$p_T$ tail observables at the LHC offer a complementary probe to low-energy experiments for studying the flavor structure of the Standard Model and beyond. We discuss the high-$p_T$ tails of neutral- and charged-current Drell-Yan processes to probe New Physics (NP) effects in semileptonic transitions. For this purpose, we describe the relevant cross-sections in terms of general form-factors, which are matched to the Standard Model Effective Field Theory (SMEFT), or to new resolved bosonic mediators arising in ultraviolet models. Using the latest run-2 datasets from LHC on the relevant mono-lepton and di-lepton production channels, we derive constraints on the SMEFT Wilson coefficients and the NP coupling constants. We also present the Mathematica package
HighPT, which provides a simple way to compute the relevant high-$p_T$ tail observables and to extract the complete LHC likelihood for Drell-Yan with general flavor structure. To illustrate the relevance of these results, we revisit the leptoquark explanations of the charged-current $B$-meson anomalies, by exploring the complementarity of our high-$p_T$ constraints with the relevant low-energy observables.