Aquaponics is currently undergoing a transformation into an intensive food production system. The initially applied systems focused on small-scale, fish-centric coupled (CAP, the aquaculture, and the hydroponic units are arranged in a single loop, and the water flows continuously from the fish tanks to the plant unit and back) aquaponics. More recently, the primary area of research interest has shifted toward larger-scale, plant-centric decoupled (aquaculture and hydroponics units are arranged in a multi-loop setup as separate functional units that can be controlled independently) systems, aiming to achieve greater economic benefits and employ more environmentally friendly practices. The objective of this study was to address gaps in the expansion of decoupled larger-scale aquaponics and to provide a comprehensive understanding of the water and nutrient flow in the system. For this purpose, experiments were performed in a greenhouse on CAP and DCAP systems, while this study also included measurements in a pure hydroponic system (HP). This study presents an assessment of the water and nutrient flow in four different crops: basil; cucumber; parsley; and tomato, all co-cultivated with a tilapia aquaculture system. Significant nutrient deficiencies and imbalances were identified in the CAP solution, leading to pronounced impacts on nutrient assimilation, particularly for fruiting vegetables. However, the average nutrient use efficiency (NUE) for nitrogen, phosphorous, potassium, and calcium was found to be 42% higher in the CAP treatment compared to HP and DCAP treatments. The nutrient solution in the DCAP treatment did not exhibit differences in water quality parameters and nutrient efficiency when compared to HP, resulting in similar effects on nutrient assimilation. Nonetheless, it was observed that DCAP plants exhibited superior NUE compared to HP plants.