The present study was conducted to explore the role of different types of vermicomposts (VCs) prepared from different substrates to improve soil health (physical and chemical properties) and wheat plant growth under field conditions. Different combinations of vermicompost prepared from different substrates (cow dung, paper waste, and rice straw) and inorganic fertilizers were applied in soil using wheat as a test plant. The impact of three different VCs on physico-chemical characteristics and nutrient availability in soil was evaluated to examine their efficacy in combination with chemical fertilizers. Temporal trends in vermicomposting treatments at various stages showed significant improvement in physico-chemical attributes of the VCs substrates. All the plant physiological attributes showed significant response where N:P:K 100:50:50 kg ha −1 + 10 t ha −1 cow dung vermicompost was applied. In addition, post-harvest analysis of soil not only revealed that different combinations of the vermicomposting treatments improved the soil health by improving the physico-chemical attributes of the soil. Conclusively, application of cow dung vermicompost along with recommended NPK not only improved crop yield, soil health, reduced insect (aphid) infestation but also fortified grains with Zn and Fe. Funding acquisition, Z.A., S.B. and M.M.; Investigation, Z.A. and W.H.; Methodology, N.A., N.K.N. and M.I.K.; Resources, M.M.; Supervision, K.B. and Z.C.; Validation, N.A. and N.K.N.; Writing-original draft, S.B.; Writing-review & editing, K.B., Z.C. and M.M.