The rice-wheat system (RWS), managed over 10.5 Mha in the Indo-Gangetic Plains of India suffers from production fatigue caused by declining soil organic matter, multi-nutrient deficiencies and diminishing factor productivity. We, therefore, conducted a long-term field experiment (1998⁻1999 to 2017⁻2018) in Modipuram, India to study the effect of continuous use of farmyard manure (FYM) as an organic fertilizer (OF), mineral fertilizers applied alone (RDF) and their combination (IPNS), as well as the inclusion of forage berseem (IPNS+B) or forage cowpea (IPNS+C) on crop yield, soil health and profits. The long-term yield trends were positive (p < 0.05) in all treatments except the control (unfertilized) in rice, and the control and RDF in wheat. Although the yields of rice, wheat and RWS were highest under IPNS treatments (IPNS, IPNS+B, IPNS+C), the maximum annual yield increase in rice (9.2%) and wheat (13.7%) was obtained under OF. A linear regression fitted to the yield data under different IPNS options revealed a highly significant (p < 0.001) annual yield increase in rice (5.1 to 6.6%) and wheat (6.8 to 7.7%) crops. Continuous rice-wheat cropping with RDF brought an increase in soil bulk density (Db) over the initial Db at different soil profile depths, more so at depths of 30⁻45 cm, but inclusion of forage cowpea or berseem in every third year (IPNS+B or C) helped to decrease Db, not only in surface (0⁻15 cm) but also in sub-surface (15⁻30 and 30⁻45 cm depth) soil. Whereas soil organic carbon (SOC) increased under OF, IPNS and IPNS + legume (B or C) treatments, it remained unaffected under RDF after 20 RW cycles. The inclusion of legumes along with IPNS not only helped to trap the NO3⁻N from soil layers below 45 cm but also increased its retention in the upper soil (0⁻15 cm depth). On the other hand, RDF had a higher NO3⁻N content in the lower layers (beyond 45 cm depth), indicating downward NO3⁻N leaching beyond the root zone. A build-up of Olsen-P was noticed under RDF at different time intervals. The soil exchangeable K and available S contents were maximal under OF and IPNS options, whereas a decline in DTPA extractable-Zn was recorded under OF. Overall, RWS economics revealed that OF treatment involved the maximum cost of cultivation (US$1174 ha−1) with the least economic net return (US$1211 ha−1). Conversely, IPNS + legume (B or C) had lowest cost of cultivation (US$707 to 765 ha−1) and a significantly higher (p < 0.05) net return (US$2233 to 2260 ha−1). The study, thus, underlines the superiority of IPNS over RDF or OF; the inclusion of legumes gives an added advantage in terms of production sustainability and soil health. Further studies involving IPNS ingredients other than FYM is needed to develop location-specific IPNS recommendations.