Aquaponics, integrating hydroponics and aquaculture in a circular system, offers a promising approach to addressing food and nutrition security while promoting water conservation in South Africa. This technology is a sustainable means of food production that minimizes environmental waste by simultaneously cultivating plants and rearing fish. This study aimed to evaluate the histology of muscle tissue in Mozambique tilapia (Oreochromis mossambicus) and the performance of Irish potato (Solanum tuberosum) in a small-scale sandponics system. Two potato cultivars (Moonlight and Taurus) were planted in a system linked to a 1000-L water tank containing 25 sexually mature Mozambique tilapia from January to June 2023. Fish histology and potato yield performance were assessed to gauge the efficiency of the system and to generate baseline data for future studies. Results showed that tuber production in the sandponics system was comparable to field conditions, with the Moonlight cultivar yielding the heaviest tubers (293-307 g per plant) with a short-oval shape, demonstrating its superior adaptability to this system. Taurus yielded lighter tubers (139-168 g per plant) that were either round or short oval depending on the grow beds used for production. Fish histological analysis revealed a higher prevalence of muscle tissue alterations in the control group compared to the experimental group. However, both groups displayed a similar condition factor (p < 0.05), indicating good overall health. Despite the promising results, the significantly high levels (p < 0.05) of metal accumulation (As, Cu, Mn, and Zn) in the fish were observed, raising concerns about their suitability for human consumption. This study demonstrates that sandponics systems can effectively support potato production with fish maintaining good general health. However, further investigation is needed to mitigate metal accumulation to ensure the safety of fish for consumption.