In carbon storage activities, and in shale oil and gas extraction (SOGE) with carbon dioxide (CO2) as stimulation fluid, CO2 comes into contact with shale rock and its pore fluid. As a reactive fluid, the injected CO2 displays a large potential to modify the shale’s chemical, physical, and mechanical properties, which need to be well studied and documented. The state of the art on shale–CO2 interactions published in several review articles does not exhaust all aspects of these interactions, such as changes in the mechanical, petrophysical, or petrochemical properties of shales. This review paper presents a characterization of shale rocks and reviews their possible interaction mechanisms with different phases of CO2. The effects of these interactions on petrophysical, chemical and mechanical properties are highlighted. In addition, a novel experimental approach is presented, developed and used by our team to investigate mechanical properties by exposing shale to different saturation fluids under controlled temperatures and pressures, without modifying the test exposure conditions prior to mechanical and acoustic measurements. This paper also underlines the major knowledge gaps that need to be filled in order to improve the safety and efficiency of SOGE and CO2 storage.