This study delves into the intrinsic and multiphase flow properties, specifically steady-state drainage relative permeability, of a subsurface Deadwood sandstone from the Aquistore CO2 storage site in Canada. Consecutive core-flooding experiments were conducted utilizing N2- and scCO2-brine pairs across a broad range of temperatures (20–70 °C) and isotropic effective stress (0–30 MPa). Moreover, we monitored crack initiation and propagation of the sandstone during uniaxial loading at an elevated temperature using an integrated approach that combines microCT scanning with an in-situ heating/loading test. Our findings reveal a 54 % decrease and a 3 % increase in the absolute permeability of the sandstone through isothermal compaction followed by thermal expansion processes, respectively. Elevating the temperature from 20 °C to 70 °C results in a systematic 24 % increase in irreducible brine saturation and nearly doubles the end-point N2 mobility, indicating an increased tendency of the rock surface towards the brine phase with temperature. Substituting N2 with scCO2 demonstrates a leftward shift in relative permeability and a decrease in irreducible brine saturation (from 0.36 to 0.31), consistent with low interfacial tension and the de-wetting effect during cyclic scCO2-brine injections. Micro-CT image analysis reveals micro-crack initiation at 10 MPa stress and 70 °C temperature, suggesting that a mixed impact of induced cracks, dynamic wettability, and thermo-mechanical deformation is responsible for the substantial increase in well injectivity over time in Aquistore. This novel experimental program provides indispensable insight into thermo-poromechanical and wettability controls on multiphase flow at the Aquistore injection site in Canada, with potential applicability to similar scenarios globally.