Cancer remains a global health challenge, with 19.3 million new cases and 10 million cancer-related deaths reported in 2020. Despite advancements in radiation, chemotherapy, and surgical treatments, limitations such as poor drug specificity, toxicity, and resistance hinder their effectiveness. Emerging strategies, including the development of smart drug delivery systems (SDDS) and tumor-homing peptides, offer a promising alternative by enhancing drug efficacy while minimizing side effects. Tumor-homing peptides, through selective targeting and internalization, enable precise delivery of therapeutic agents to tumor cells, improving therapeutic outcomes. Nanotechnology has further revolutionized drug delivery systems, providing stimuli-responsive platforms for enhanced targeting. Additionally, the tumor microenvironment (TME) has been recognized as a crucial factor influencing cancer progression and therapy response. This chapter highlights the role of peptides in addressing key challenges in cancer therapy, including targeting tumor vasculature, extracellular matrix, lymphatic vessels, and cell membranes, while also presenting innovative strategies for drug delivery and therapeutic intervention.