In the context of energy transition and carbon emission reduction, Carbon Capture, Utilization, and Storage (CCUS) has emerged as a critical technological pathway. CO2 flooding in low-permeability reservoirs offers the dual benefits of enhanced oil recovery and carbon sequestration. However, its production dynamics are inherently non-stationary and strongly coupled across wells due to phase transitions and gas breakthrough phenomena. Existing approaches, including compositional simulations and data-driven models, either suffer from prohibitive computational costs or fail to ensure physically consistent predictions under complex multiphase conditions. To address this issue, an end-to-end learning and optimization framework is proposed by integrating a Physics-Inspired Graph Network (PIGN) with the multi-objective optimization algorithm NSGA-II. The framework is trained on datasets generated from numerical simulations under multiple geological realizations, with well properties, inter-well connectivity, and production schemes as inputs. Spatial–temporal dynamics are captured through a hybrid architecture combining TAGConv with GRU/LSTM modules. A multi-head independent output structure is designed to separately predict gas, oil, water, and CO2 production, while well embeddings are introduced to characterize inter-well heterogeneity. Furthermore, physics-inspired constraint losses based on local trend variations, derivative responses, and smoothness are incorporated to achieve a hybrid modeling paradigm that integrates data-driven learning with physical consistency. The surrogate model is further embedded into the NSGA-II framework, where CO2 sequestration and cumulative oil production are treated as competing objectives, enabling integrated optimization of CO2 flooding and storage. Results demonstrate that, compared with GNN-GRU, LSTM, GRU, and TCN, the proposed PIGN reduces the overall MAPE by approximately 13.0%, 23.0%, 24.3%, and 31.6%, respectively. Specifically, PIGN achieves error reductions of approximately 0.8%–1.5% in gas prediction, 1.0%–10.7% in water prediction, and 19.8%–44.4% in CO2 prediction compared to baseline models. Multi-objective optimization results indicate that the knee-point solution achieves approximately a 7.5% increase in cumulative oil production and a 4.9% increase in CO2 sequestration compared to the baseline strategy. These results validate the effectiveness of the proposed method in modeling complex multiphase dynamics and optimizing production strategies.