Background: Cancer-related hospitalizations constitute one of the primary drivers of cancer-related healthcare expenses. Understanding the burden and characteristics of these hospitalizations is essential to appropriately direct resources, improve outcomes, and avoid unnecessary hospitalizations. Our study sought to evaluate the national trends, reasons, disposition status, length of stay, and associated costs for cancer-related hospitalizations. Methods: We conducted a retrospective analysis of cancer hospitalizations using the 2008-2019 National Inpatient Sample. Cancer-related hospitalizations were identified using validated Clinical Classification Software (CCS) codes 11 to 45. Trends in hospitalization volume, mortality, length of stay, disposition status, and costs were analyzed overall and by cancer type, adjusted according to the US Consumer Price Index. Results: There were 371 million weighted hospitalizations from 2008 to 2019, of which 15.1% (56 million) were cancer related. The most reported cancer types were breast cancer (11.9%), secondary malignancies (11.2%), and prostate cancer (10.3%). The most common reasons for cancer-related hospitalizations were septicemia (4.8%), pneumonia (4.7%), and complications of surgical procedures or medical care (3.1%). Trend analysis showed that the total number of cancer-related hospitalizationsincreased from 12,963 to 16,500 per 100,000 hospitalizations during the study period (relative increase, 27.3%). Mortality rates decreased from 5.1% to 4.0% (relative decrease, 21.6%), while the length of stay decreased from 3.5 to 3.2 days (relative decrease, 8.6%) during the study period. Disposition to home or short-term facilities decreased (relative decrease, 3.1%), while to long-term facilities increased (relative increase, 20.6%) during the same period. Total hospitalization cost increased from $55.5 billion in 2008 to $76.4 billion in 2019 (a relative increase of 37.7%). Conclusions: Our analysis shows that while cancer-related hospitalizations and associated costs increased substantially, mortality rates, and length of stay decreased. These trends reflect rising cancer burden but improvements in hospital cancer care quality and efficiency. Ongoing efforts to optimize cancer treatment, minimize unnecessary hospitalizations, reduce length of stay, and facilitate safe discharges are needed to improve patient outcomes and control costs further. Continued surveillance and health policies should address the rising demand for high-value cancer care.