Cancer remains a complex and life-threatening disease, and mortality is projected to increase significantly by 2060. Current therapeutic modalities such as chemotherapy, radiation therapy, and surgical interventions are challenged by drug resistance and adverse effects, necessitating the development of innovative strategies. Nanotechnology-based drug delivery systems, particularly stimuli-responsive polymeric vesicles, present a promising avenue for advancing cancer treatment. These systems increase efficacy and safety by improving drug bioavailability, targeting, and payload protection. Polymersomes are vesicular structures that are hollow and surrounded by bilayer membranes formed by the self-assembly of amphiphilic block copolymers. Their tunable mechanical robustness, encapsulation capacity, and easy surface modification make them attractive candidates for next-generation drug delivery systems. In this chapter, we have explored the versatility of stimuli-responsive polymersomes in cancer therapy. It provides an overview of the structure and formation mechanisms (including solvent-free and solvent-displacement methods) and the advantages and limitations of each approach for controlling size, morphology, and encapsulation efficiency. The key properties that distinguish polymersomes from classical liposomes are critically analyzed. The focus on stimuli-responsive drug release strategies allows the spatiotemporal control of drug delivery to tumor microenvironments. This chapter reviews preclinical studies showing the efficacy of polymersomes in cancer models, including enhanced tumor accumulation and therapeutic efficacy. Challenges hindering clinical translation, including biocompatibility, stability, scalability, and regulatory barriers, are also addressed. Future research directions, including multistimuli-responsive systems, combination therapies, and personalized nanomedicine approaches, are also explored. The potential of polymersomes to advance cancer treatment was critically assessed, emphasizing their capacity to enable precise drug delivery, reduce off-target effects, and address drug resistance. However, the evaluation also underscores the necessity for further research to fully establish their clinical applicability.