Background: Tumors of the pineal region account for less than 1% of supratentorial neoplasms in adults and represent a distinct neuro-oncological challenge. Their management requires a multidisciplinary and multimodal approach. Traditionally, direct surgical resection was considered the primary treatment modality. Recent advances in minimally invasive techniques and onco-radiotherapy have paved the way for safer and more personalized treatment strategies, in line with the principles of precision medicine. This study aims to present our institutional approach, which relies on a combination of endoscopic and radiotherapy-based techniques. Methods: A retrospective, single-center clinical study was conducted involving 28 adult patients who underwent endoscopic third ventriculostomy and biopsy of a pineal region tumor between January 2014 and March 2025. Descriptive statistics, permutation tests with bootstrap-derived confidence intervals, Fisher’s exact test, and Kaplan–Meier survival analysis were applied for data evaluation. Results: Endoscopic intervention resulted in clinical improvement in 78% of cases. A significant increase in performance status was observed in the postoperative period (<0.001) compared to preoperative results. Radiotherapy contributed to either tumor regression or disease stabilization. Conclusions: Based on our findings, the combination of endoscopic intervention and personalized radiotherapy represents a safe and effective treatment strategy, offering a compelling alternative to direct surgical resection, which is reserved as a second-line treatment.