Cotton is a cash crop of arid to semiarid regions, and the present study investigates the integration of biofertilizers with organic amendments and balanced NPK for improving cotton growth, yields, nutritional quality, antioxidant status and soil health. Two local cotton varieties (SS32 and CK9) were evaluated in a completely randomized design (CRD) with three replications in pots. Treatments include control, recommended NPK, compost, poultry manure, biofertilizer +NPK, biofertilizer +compost +NPK and biofertilizer +poultry manure +NPK. The results revealed a significant improvement in cotton growth, nutritional and yield attributes viz., shoot length by 26 and 29%, root length by 28 and 29%, seed cotton yield by 28 and 34%, lint yield by 32 and 38%, shoot nitrogen by 26 and 32%, phosphorus by 31 and 33%, K by 26 and 29%, Zn by 33 and 34% and Fe by 27 and 34% under CK9 and SS32, respectively, by biofertilizer +compost +NPK treatment compared to control. Same treatment also improved microbial biomass carbon (MBC) by 45% and 43%, and CFU by 36% and 28%, under the CK9 and SS32 varieties, respectively. It can be concluded that integrating different nutrient sources offers sustainable cotton production while improving soil quality.