Aerosol-cloud interaction is recognized as one of the key factors influencing cloud properties and precipitation regimes across local, regional, and global scales and remains one of the largest uncertainties in understanding and projecting future climate changes. Deep convective clouds (DCCs) play a crucial role in the general circulation, energy balance, and hydrological cycle of our climate system. The complex aerosol-DCC interactions continue to be puzzling as more “aerosol effects” unfold, and systematic assessment of such effects is lacking. Here we systematically assess the aerosol effects on isolated DCCs based on cloud-resolving model simulations with spectral bin cloud microphysics. We find a dominant role of vertical wind shear in regulating aerosol effects on isolated DCCs, i.e., vertical wind shear qualitatively determines whether aerosols suppress or enhance convective strength. Increasing aerosols always suppresses convection under strong wind shear and invigorates convection under weak wind shear until this effect saturates at an optimal aerosol loading. We also found that the decreasing rate of convective strength is greater in the humid air than that in the dry air when wind shear is strong. Our findings may resolve some of the seemingly contradictory results among past studies by considering the dominant effect of wind shear. Our results can provide the insights to better parameterize aerosol effects on convection by adding the factor of wind shear to the entrainment term, which could reduce uncertainties associated with aerosol effects on climate forcing.