A new approach for an eco-friendly multi-functionalization of cotton/wool (C/W) and viscose/wool (V/W) blended fabrics was investigated. In this study, Ag-nanoparticle (Ag-NP) and/or ZnO-nanoparticle (ZnO-NP) functional agents were incorporated into the finishing bath along with citric acid (CA) or succinic acid (SA) as ester-crosslinking or esterifying agent, and sodium hypophosphite catalyst using the padding technique. The obtained results indicated that the extent of multi-functionalization expressed as antibacterial activity, UV-blocking functionality and wrinkle recovery ability were determined by kind of nanomaterial, nature of carboxylic acid, i.e., bi- or tri-functional and type of substrate. The results also demonstrated that blended fabrics finished with Ag-NP/ZnO-NP/CA/SHP nano-finishing formulation exhibited outstanding durable multi-functional properties even after 10 washing cycles. In addition, the change in surface morphology and the existence of Ag and/or Zn onto the selected V/W fabric surfaces have been confirmed by SEM and EDX analysis respectively.