Cancer stem cells (CSCs) have considerable pivotal attention in the research field of oncology due to their unique characteristic features that assume their potential as cancer therapeutic targets. Self-renewal, infinite proliferation, and replication are among their stem cell–like features that are responsible for cancer recurrence even after chemotherapy and radiotherapy. Thus, targeting both intrinsic and extrinsic anti-apoptotic pathways for eradicating CSCs is a promising therapeutic approach for decreasing cancer morbidity and mortality. This chapter aims to provide an in-depth summarized exploration of CSCs’ robust features and their clinical implications, addressing challenges and future prospects of their therapeutic potential in the most recent context of cancer-targeted therapies.