The tumor-targeted drug delivery system (TTDNS) uses nanocarriers to transport chemotherapeutic agents to target tumor cells or tissues precisely. This innovative approach considerably increases the effective concentration of these drugs at the tumor site, thereby enhancing their therapeutic efficacy. Many chemotherapeutic agents face challenges, such as low bioavailability, high cytotoxicity, and inadequate drug resistance. To address these obstacles, TTDNS comprising natural polysaccharides have gained increasing popularity in the field of nanotechnology owing to their ability to improve safety, bioavailability, and biocompatibility while reducing toxicity. In addition, it enhances permeability and allows for controlled drug delivery and release. This review focuses on the sources of natural polysaccharides and their direct and indirect mechanisms of anti-tumor activity. We also explored the preparation of various polysaccharide-based nanocarriers, including nanoparticles, nanoemulsions, nanohydrogels, nanoliposomes, nanocapsules, nanomicelles, nanocrystals, and nanofibers. Furthermore, this review delves into the versatile applications of polysaccharide-based nanocarriers, elucidating their capabilities for in vivo targeting, controlled release, and responsiveness to endogenous and exogenous stimuli, such as pH, reactive oxygen species, glutathione, light, ultrasound, and magnetic fields. This sophisticated design substantially enhances the chemotherapeutic efficacy of the encapsulated drugs at tumor sites and provides a basis for preclinical and clinical research. However, the in vivo stability, drug loading, and permeability of these preparations into tumor tissues still need to be improved. Most of the currently developed biomarker-sensitive polysaccharide nanocarriers are still in the laboratory stage, more innovative delivery mechanisms and clinical studies are needed to develop commercial nanocarriers for medical use.