This study aimed to evaluate the efficiency of an integrated multi-trophic aquaculture (IMTA) system comprising co-cultured fed fish and organic extractive species representing three distinct trophic levels as well as the impact and potential utilization of two commercially available fish feeds made up of 35% fish meal (FM) and 20% fish meal (LFM) ingredients, using a multi-indicator assessment approach. Significant alterations were observed in growth performance indicators (GPIs), water and sediment quality indices, toxicity tests and biomarkers within the IMTA system. The fish survival, weight gain (WG), and specific growth rate (SGR) were higher in the IMTA system with significantly lower feed conversion ratios (FCRs) and higher feed efficiency (FE) in comparison to the fed fish monoculture system. Yet, organic filter feeders displayed 100% survival, and increased shell growth, while deposit feeders exhibited successful survival and significant weight gain. In the comparison between FM-IMTA and LFM-IMTA, fed fish in FM-IMTA showed higher WG, SGR, and FE with lower FCR. Environmental parameters like temperature, oxygen, and nutrient concentrations fluctuated but generally improved in the IMTA system, indicating lower mesotrophic conditions. Sediment fatty acid profiles differed between systems and toxicity assessments, which suggested a lower impact in IMTA and FM-IMTA systems. The sediment microbial community displayed high similarity within IMTA systems and between FM-IMTA and LFM-IMTA. These findings underscore the potential of IMTA systems for sustainable aquaculture, emphasizing improved growth performance and reduced environmental impact, particularly when using fish meal feeds.