A model based on first principles is presented to compute nucleate boiling heat transfer coefficients. It includes microscale heat and mass transfer phenomena in the so-called micro region, i.e., the thin film area where the liquid vapor phase interface approaches the wall. The model is verified by comparing calculated to measured heat transfer coefficients. Parameter studies allowed to identify physical phenomena governing the typical reduction of binary mixture heat transfer coefficients compared to the ideal heat transfer coefficient, i.e., the molar average of the heat transfer coefficients of the two pure components of the mixture. These are bubble site density and departure diameter that deviate from the corresponding values of the two pure components. Furthermore, overall heat transfer is decreased by strong concentration gradients in the micro region.