Understanding how marine diatoms adapt to elevated CO2 and warming over evolutionary timescales is crucial for predicting future marine ecosystem dynamics. Using multi-omics approaches, we explored the genomic, transcriptomic, epigenetic, and metabolomic responses of Thalassiosira weissflogii and Phaeodactylum tricornutum to high CO2 and/or warming and examined how these changes influence trophic transfer to secondary producers. Genomic analyses revealed that warming caused greater genetic diversity loss and differentiation than high CO2 alone. However, when combined, high CO2 moderated the diversity loss driven by warming, suggesting that CO2 mitigates the evolutionary pressures of warming. These genomic changes underpin the diatoms' long-term adaptation to global change. Transcriptomic data showed that warming had a more substantial impact on gene expression than elevated CO2, with the highest number of differentially expressed genes (DEGs) observed under combined conditions. Key metabolic pathways, such as ribosome biosynthesis and energy metabolism, were upregulated to counter reduced photosynthesis efficiency under stress. Epigenetically, DNA methylation acted in concert with gene expression to regulate adaptive responses. In Phaeodactylum tricornutum, methylation in gene bodies correlated positively with expression, particularly in genes involved in central metabolism, ribosome biogenesis, and terpenoid biosynthesis. This suggests that DNA methylation plays a critical role in long-term adaptation to environmental changes. Metabolomic profiling revealed that warming downregulated terpenoid backbone biosynthesis in Phaeodactylum tricornutum, leading to reductions in pyruvate levels and changes in phenylalanine metabolism. These metabolic alterations were transferred to the secondary producer, the clam Coelomactra antiquata, resulting in decreased pyruvate and pyruvaldhyde and increased 2-hydroxylamino-4,6-dinitrotoluene in the clam. Our study provides integrated insights into how marine diatoms adapt to global change from a molecular perspective and how these adaptations affect trophic transfer across food webs. These findings offer a clearer understanding of how future ocean conditions may reshape marine ecosystem structure and function, with broad implications for ecosystem services and biodiversity.