Aquaculture is the fastest-growing food production sector globally; however, its expansion is constrained by its reliance on finite and unsustainable feed ingredients, such as fishmeal and fish oil. This chapter explores the paradigm shift from traditional, empirical feed formulation to a new era of precision nutrition, driven by high-throughput omics technologies. It details how genomics, transcriptomics, proteomics, metabolomics, and microbiomics constitute a powerful analytical toolbox for revolutionizing every stage of feed development. This journey begins with the deep molecular evaluation of alternative raw materials, including plant-based proteins, insect meals, and algal or single-cell proteins and extends to the rational design and validation of functional feeds. These sophisticated formulas are designed not only for growth but also to actively regulate host physiology, improving immunity, gastrointestinal health, and stress resilience. We demonstrate how omics elucidates the intricate molecular relationships between diet and host through species-specific case studies on commercially significant groups such as carps, tilapia, salmon, and shrimp, identifying novel biomarkers for performance and health. Finally, we explore the next frontier, where multi-omics data integration with artificial intelligence and machine learning facilitates data-driven feed optimization systems, ultimately aiming for personalized aquafeeds tailored to an animal’s specific genotype, life stage, and environment. This omics-driven methodology is essential for guaranteeing the economic and environmental sustainability of the global aquaculture sector, enabling it to address future food security challenges.