This chapter examines the intricate relationship between radiotherapy (RT) and surgery in the management of pediatric cancer, emphasizing the significant role that RT plays in both curative and palliative treatment strategies. Pediatric cancers present unique challenges due to the biological differences between pediatric and adult malignancies, and the impact of RT on long-term development and health. The chapter explores key concepts in radiation oncology that are essential for surgeons, such as clinical target volume, gross tumor volume, and advanced RT techniques like intensity-modulated radiation therapy and proton beam therapy. Additionally, the chapter discusses how RT affects surgical decision-making, timing, and techniques, highlighting the complexities of integrating RT with surgery, particularly in areas such as tissue fibrosis, vascular damage, and delayed wound healing. The impact of RT on the surgical resection of tumors, especially in previously irradiated tissues, is also considered, along with the importance of accurate staging and the surgeon’s role in radiation planning. Further, the chapter addresses the timing of RT relative to surgery, exploring the benefits and challenges of preoperative and postoperative RT, and the optimal sequencing for various pediatric cancers. Finally, the long-term effects of RT on surgical outcomes are reviewed, underscoring the importance of minimizing radiation-induced toxicities to improve the quality of life and overall survival of pediatric cancer patients. This chapter emphasizes the need for a multidisciplinary approach, where careful planning, coordination, and timing between surgery and RT are crucial for optimizing treatment outcomes and minimizing risks.