Compared with North American marine crude oils characterized by high light hydrocarbon contents, the continental crude oils from Shengli Oilfield are predominantly composed of medium and heavy fractions. High-pressure CO2 miscible flooding stands as one of the pivotal CCUS-EOR technologies for enhancing the recovery efficiency of such medium-heavy crude oils. Systematically unraveling the miscibility mechanism between CO2 and crude oil, along with quantitatively assessing the miscibility degree of different oil components and their response patterns to the key parameters of pressure and temperature, is of profound significance for deepening the understanding of high-pressure miscible flooding mechanisms and optimizing engineering implementation pathways. In this study, molecular dynamics (MD) simulation approaches were employed to investigate the miscibility behaviors between CO2 and model alkane oils with varying carbon chain lengths under different pressure and temperature conditions. First, a quantitative evaluation method for miscibility degree was established based on the physical essence of miscible extraction, which enabled the revelation of the response laws of miscibility degree for different pseudo-components of crude oil to temperature and pressure variations. Second, the thermodynamic and kinetic mechanisms underlying the miscibility process were clarified by analyzing three core aspects: the intermolecular interactions between CO2 and hydrocarbon molecules (miscibility driving force), the cohesive forces among hydrocarbon molecules themselves (miscibility resistance), and the diffusion behaviors of hydrocarbon molecules. Furthermore, key controlling parameters, including coordination number, diffusion coefficient, and the slope of the driving-to-resistance force ratio, were extracted to construct a kinetic model describing CO2-hydrocarbon miscibility in crude oil systems. The miscibility degree predicted by the proposed model shows excellent consistency with the results derived from MD simulations and is well-corroborated by experimental data from high-pressure extraction tests, thus verifying the model’s applicability and reliability. This established CO2-hydrocarbon miscibility kinetic model not only clarifies the intrinsic physical mechanisms and dominant controlling factors governing enhanced oil recovery via high-pressure CO2 miscible flooding, but also exhibits favorable expandability of its core paradigm and potential for cross-block transplantation. It thereby provides robust theoretical support and parameter basis for the design and optimization of field-scale CO2 flooding schemes.