Polymer-based drug delivery systems (DDSs) are increasingly used in cancer therapy to enhance drug targeting, improve therapeutic efficacy, and reduce side effects. This review discusses the barriers that impact the success of chemotherapy drug delivery and recent developments in natural and synthetic polymer-based DDSs for cancer treatment. Chemotherapy, often combined with surgery and radiotherapy, is a common treatment for cancer, but its off-target effects can lead to significant side effects and dose-limiting toxicities. To address these challenges, polymer-based DDSs have been developed to improve drug delivery, targeting, and therapeutic outcomes. Natural and synthetic polymers offer advantages such as biodegradability, biocompatibility, and physicochemical stability, making them ideal for drug delivery. These polymers can facilitate selective targeting, enhance drug circulation, improve delivery, and provide controlled release through various mechanisms. For example, poly(lactic glycolic acid) (PLGA) is a biodegradable polymer that has been approved by the U.S. FDA for cancer treatment. Other natural polymers, such as chitosan, hyaluronic acid, alginate, cellulose, and gelatin, have also been explored for their potential in drug delivery. These polymers can be modified to enhance their properties, such as solubility, stability, and targeting capabilities. Synthetic polymers, including poly(ethylene glycol) (PEG), poly(caprolactone), and poly(ethyleneimine), are also used in DDSs due to their ability to be modified for specific functions. PEGylation, for instance, improves the stability and circulation time of drugs by reducing immunogenicity and enhancing blood circulation. However, PEGylation can also lead to reduced bioactivity and the formation of anti-PEG antibodies, which may accelerate drug clearance. Polymer-based DDSs have shown promise in overcoming the limitations of traditional chemotherapy by improving drug delivery to tumor sites, enhancing therapeutic efficacy, and reducing side effects. These systems can be designed to target specific receptors on cancer cells, improve drug uptake, and enhance the effectiveness of immunotherapy. Despite their potential, challenges such as drug loading capacity, stability, and manufacturing remain important considerations in the development of effective delivery systems. In conclusion, polymer-based DDSs offer a promising approach for improving cancer therapy by enhancing drug delivery, targeting, and therapeutic outcomes. These systems have the potential to overcome the challenges associated with traditional chemotherapy and provide more effective and safer treatment options for cancer patients.Polymer-based drug delivery systems (DDSs) are increasingly used in cancer therapy to enhance drug targeting, improve therapeutic efficacy, and reduce side effects. This review discusses the barriers that impact the success of chemotherapy drug delivery and recent developments in natural and synthetic polymer-based DDSs for cancer treatment. Chemotherapy, often combined with surgery and radiotherapy, is a common treatment for cancer, but its off-target effects can lead to significant side effects and dose-limiting toxicities. To address these challenges, polymer-based DDSs have been developed to improve drug delivery, targeting, and therapeutic outcomes. Natural and synthetic polymers offer advantages such as biodegradability, biocompatibility, and physicochemical stability, making them ideal for drug delivery. These polymers can facilitate selective targeting, enhance drug circulation, improve delivery, and provide controlled release through various mechanisms. For example, poly(lactic glycolic acid) (PLGA) is a biodegradable polymer that has been approved by the U.S. FDA for cancer treatment. Other natural polymers, such as chitosan, hyaluronic acid, alginate, cellulose, and gelatin, have also been explored for their potential in drug delivery. These polymers can be modified to enhance their properties, such as solubility, stability, and targeting capabilities. Synthetic polymers, including poly(ethylene glycol) (PEG), poly(caprolactone), and poly(ethyleneimine), are also used in DDSs due to their ability to be modified for specific functions. PEGylation, for instance, improves the stability and circulation time of drugs by reducing immunogenicity and enhancing blood circulation. However, PEGylation can also lead to reduced bioactivity and the formation of anti-PEG antibodies, which may accelerate drug clearance. Polymer-based DDSs have shown promise in overcoming the limitations of traditional chemotherapy by improving drug delivery to tumor sites, enhancing therapeutic efficacy, and reducing side effects. These systems can be designed to target specific receptors on cancer cells, improve drug uptake, and enhance the effectiveness of immunotherapy. Despite their potential, challenges such as drug loading capacity, stability, and manufacturing remain important considerations in the development of effective delivery systems. In conclusion, polymer-based DDSs offer a promising approach for improving cancer therapy by enhancing drug delivery, targeting, and therapeutic outcomes. These systems have the potential to overcome the challenges associated with traditional chemotherapy and provide more effective and safer treatment options for cancer patients.