The development of targeted anti-cancer therapies is a critical area of research, aiming to overcome the limitations of conventional treatments that often cause severe side effects and damage to healthy cells. In this study, we report the synthesis and characterization of a novel, smart nanoparticle-based drug delivery system designed for enhanced cancer cell targeting. Specifically, niosomes were surface-functionalized with a dual-modified chitosan (CS) incorporating folic acid (FA) and hyaluronic acid (HA), targeting receptors that are commonly overexpressed on cancer cells. Importantly, the modification preserved free amino groups on the CS backbone, enabling pH responsiveness in acidic environments such as the tumor microenvironment. This design confers the system with triple targeting capabilities: receptor-mediated (FA and HA) and pH-sensitive (CS) targeting. Two bioactive compounds were co-encapsulated within the niosomes: hydrophobic curcumin, known for its anti-cancer properties, and hydrophilic ascorbic acid (10 mg/mL), offering potential synergistic therapeutic effects. FTIR analysis confirmed the successful dual modification of CS with FA and HA, its effective coating onto the niosomes, and the presence of unmodified amino groups. Dynamic light scattering (DLS) analysis demonstrated optimal formulation with cholesterol and surfactants (Span 60 and Tween 60 at a 0.2:1:1 ratio), producing unloaded niosomes of 101 nm in diameter. Surface coating with modified CS increased the particle size to 174.5 nm, with further size increase upon drug encapsulation. Scanning electron microscopy (SEM) revealed a morphology suitable for cellular uptake, while in vitro cytotoxicity studies confirmed enhanced efficacy against cancer cells. The proposed multifunctional niosomal system exhibits promising features for targeted anticancer therapy, combining receptor-specificity, pH responsiveness, and synergistic drug action for improved therapeutic outcomes.