This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized by the Warburg effect, and the dynamic interplay between cancer cells and mitochondria. It also examines the role of cancer stem cells (CSCs) in treatment resistance and the regulatory influence of non-coding RNAs such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs). The chapter emphasizes future directions, including advancements in immunotherapy, strategies to counter adaptive resistance, integration of artificial intelligence for predictive modeling, and the identification of biomarkers for personalized treatment. The comprehensive exploration of these hallmarks provides a foundation for innovative therapeutic approaches to enhance patient outcomes.This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized by the Warburg effect, and the dynamic interplay between cancer cells and mitochondria. It also examines the role of cancer stem cells (CSCs) in treatment resistance and the regulatory influence of non-coding RNAs such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs). The chapter emphasizes future directions, including advancements in immunotherapy, strategies to counter adaptive resistance, integration of artificial intelligence for predictive modeling, and the identification of biomarkers for personalized treatment. The comprehensive exploration of these hallmarks provides a foundation for innovative therapeutic approaches to enhance patient outcomes.