Cancer chemotherapy remains one of the most effective treatment strategies, but its clinical success is often limited by challenges such as poor drug bioavailability, non-specific toxicity, and drug resistance. Drug delivery systems (DDSs) have emerged as a promising solution to overcome these barriers, offering enhanced efficacy and reduced side effects. For instance, liposomal doxorubicin (Doxil^®) has significantly improved treatment outcomes in triple-negative breast cancer (TNBC) by reducing cardiotoxicity, while albumin-bound paclitaxel (Abraxane^®) enhances drug solubility and tumor targeting in glioblastoma. This review focuses on the classification of DDSs, drug loading methods, and surface functionalization strategies, which enable targeted drug delivery, controlled release, and improved cellular uptake. Additionally, we explore the integration of stimuli-responsive systems that can release chemotherapeutic agents in situ in response to endogenous or exogenous stimuli. The potential of multifunctional DDSs to combine chemotherapy with radiotherapy, phototherapy, ultrasound therapy, immunotherapy, and imaging is also discussed. Despite promising results, the clinical translation of these systems faces challenges, including manufacturing scalability, regulatory approval, and safety concerns. Future directions for the development of more efficient and personalized DDSs for cancer treatment are also proposed.