Insect-based meals have emerged as a viable global scale alternative to fish meal in aquafeed. This is mainly due to their high protein content, balanced amino acid composition, and fatty acid profile, which closely resembles that of fish meal. An 8-week trial was conducted to evaluate the growth performance, blood serum chemistry, and histomorphology of Mozambique tilapia (Oreochromis mossambicus) fed diets containing soldier termite meal as a partial substitute for fish meal. Five isonitrogenous, isolipidic, and isocaloric diets were formulated to partially replace fish meal with soldier termite meal at 0, 10, 30, 50, and 70%, labelled as D1, D2, D3, D4, and D5, respectively. The study showed that soldier termite meal could replace fish meal up to a 50% inclusion level. The growth performance and nutrient utilisation of fish fed diet D4 (50%) were comparable to fish fed the control diet. Fish fed the diet with the highest proportion of soldier termite meal (70%) showed significantly higher alanine aminotransferase and aspartate aminotransferase levels (P < 0.05). Cholesterol, triglyceride, and glucose levels were not influenced by the inclusion of soldier termite meal in the diet of Mozambique tilapia (P > 0.05). The histomorphological examination of the intestines revealed no discernible alterations. The current study has demonstrated that soldier termite meal can replace fish meal up to 50% of the feed content without inducing adverse effects on growth performance and health status of O. mossambicus. The cost-benefit analysis showed that substituting fish meal with soldier termite meal was economically sustainable.