The degradation of Lixisols in the Senegalese Peanut Basin represents a major constraint to the sustainability of agricultural systems. Integrated agrobiofortification systems, combining organic residual products (ORPs) and microbial inocula (MI), offer a promising agroecological strategy to simultaneously restore soil fertility and enhance the micronutrient content of harvested products. While their agronomic and nutritional effects are increasingly documented, their environmental impacts on soil chemical and biological properties remain poorly studied in tropical regions. This study assesses, over two consecutive contrasting seasons, the effects of combinations of ORPs — poultry litter (PL) or sewage sludge (SS) — with beneficial native microorganisms (BM) and mycorrhizal fungi — MF (Rhizophagus irregularis) — applied to two cowpea varieties (Vigna unguiculata L., Thissine and Thieye), on soil chemistry and microbial community composition (PLFA profiles) in a Lixisol from Nioro du Rip. The main results show that: (i) treatment effects on soil chemistry are driven by the type of ORP and BM—the SS_BM treatment led to the greatest increases in total C (+78%), total N (+68%), and exchangeable Ca (+93%) compared to the untreated control; (ii) microbial responses are dominated by Treatment × Variety interactions—treatments including MF increased total microbial biomass by about tenfold for Thissine, whereas Thieye remained largely unresponsive; (iii) partial redundancy analysis (pRDA) reveals that treatments indirectly restructure microbial communities via induced chemical gradients (total C, total N, Ca), rather than through a direct effect of MI; (iv) Spearman correlations confirm that soil Zn enrichment induced by ORPs translates directly into grain Zn biofortification, and that mycorrhizal fungal biomass covaries with Gram-negative bacteria and plant micronutrient status. These results highlight two mechanistically distinct pathways, with direct implications for the