Chitosan-based nanomaterials have emerged as a highly promising platform for pH-responsive targeted drug delivery in cancer therapy, leveraging their inherent biocompatibility, biodegradability, and pH-sensitive properties. This chapter explores the structural and functional attributes of chitosan, focusing on the protonation-deprotonation dynamics of its amino groups, which enable precise pH-triggered drug release in acidic tumor microenvironments. Key advancements in nanocarrier design, including crosslinking strategies, ligand functionalization (e.g., glycyrrhizin for hepatocellular carcinoma, bisphosphonates for osteosarcoma), and integration with porous materials (mesoporous silica, MOFs), are discussed, highlighting enhanced tumor targeting and reduced systemic toxicity. Applications in liver and bone cancers demonstrate improved therapeutic efficacy through controlled drug encapsulation and stimuli-responsive release mechanisms. Characterization techniques (DLS, FTIR, TEM/SEM) and toxicological considerations are reviewed, alongside the future prospect for developing multi-targeted, multi-stimuli-responsive platforms activated by internal (pH, redox, enzymes) and optional external (light, heat) cues. By addressing current challenges and opportunities, this work underscores the potential of chitosan-based nano systems to revolutionize precision oncology.