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Tin monoxide (SnO) is an interesting two-dimensional material because it is a rare oxide semiconductor with bipolar conductivity. However, the lower room temperature mobility limits the applications of SnO in the future. Thus, we system-atically investigate the effects of different layer structures and strains on the electron–phonon coupling and phonon-limited mobility of SnO. The A2u phonon mode in the high-frequency region is the main contributor to the coupling with electrons for different layer structures. Moreover, the orbital hybridization of Sn atoms existing only in the bilayer structure changes the conduction band edge and conspicuously decreases the electron–phonon coupling, and thus the electronic transport performance of the bilayer is superior to that of other layers. In addition, the compressive strain of ε =?1.0％ in the monolayer structure results in a conduction band minimum (CBM) consisting of two valleys at the Γ point and along the M–Γ line, and also leads to the intervalley electronic scattering assisted by the Eg(?1) mode. However, the electron–phonon coupling regionally transferring from high frequency A2u to low frequency Eg(?1) results in little change of mobility.