Overcoming drug resistance and toxicity remains a significant challenge in cancer therapy. Resistance arises from genetic mutations, tumor microenvironment alterations, and drug efflux mechanisms, often leading to treatment failure. Combination therapies targeting multiple pathways simultaneously are emerging as effective strategies to combat resistance. Next-generation inhibitors focus on addressing specific resistance mechanisms, enhancing treatment efficacy. Advanced drug delivery systems, such as nanoparticle-based carriers, ensure targeted delivery, reducing systemic side effects. Predictive biomarkers aid in identifying patients likely to benefit from specific therapies, enabling personalized treatment plans. By addressing these challenges, ongoing research strives to improve the effectiveness and safety of cancer treatments, ultimately enhancing patient outcomes and quality of life.