Cadmium (Cd) is a serious environmental pollutant affecting various tissues/organs in broilers and compromising their immunological function and productivity. Therefore, the current study aimed to investigate Cd-induced immunotoxicity and potential immunoprotective effect of rutin nanoparticles (RNPs) in the bursal tissue of broilers. A total number of 150 chicks from the Hubbard breed were randomly divided into 5 groups. Group I was fed on standard basal diet (SD) with normal drinking water (DW), Group II received SD containing RNPs (50mg/kg feed) with DW, Group III fed on SD and DW containing Cd (150mg/L), Group IV co-treated with rutin-enforced SD (50mg/kg diet) and DW containing Cd (150mg/L), and finally, Group V co-supplemented with RNP-enhanced SD (50mg/kg diet) DW containing Cd (150mg/L). Productive performance, economic efficiency, oxidative biomarkers, histopathological changes, and the expression level of TLR-4, HSP-70, caspase 3, NF-κB, Bcl-2, and Bax were assessed in the BF tissue. Cd led to severe production and economic losses in exposed birds with a marked surge of oxidative biomarkers, pro-inflammatory cytokines, and histopathological changes in the bursal tissue which could be explained through upregulation of the Hsp70/TLR4/NF-κB molecular pathway in the BF tissue. Meanwhile, RNPs could alleviate most of these changes and prevail optimistic immunomodulatory properties which subsequently could enhance broilers' productivity when incorporated in their diets.