This study aims to investigate the joint effects of cancer and sleep disorders on the health-related quality of life (HRQoL), healthcare resource utilization, and expenditures among US adults. Utilizing the 2018-2019 Medical Expenditure Panel Survey (MEPS) database, a sample of 25,274 participants was categorized into four groups based on cancer and sleep disorder status. HRQoL was assessed using the VR-12 questionnaire. Generalized linear model (GLM) with a log-linear regression model combined gamma distribution was applied for the analysis of healthcare expenditure data. Individuals with both cancer and sleep disorders (C+/S+) exhibited notably lower physical health (PCS) and mental health (MCS) scores-1.45 and 1.87 points lower, respectively. They also showed significantly increased clinic visits (2.12 times), outpatient visits (3.59 times), emergency visits (1.69 times), and total medical expenditures (2.08 times) compared to those without cancer or sleep disorders (C-/S-). In contrast, individuals with sleep disorders alone (C-/S+) had the highest number of prescription drug usage (2.26 times) and home health care days (1.76 times) compared to the reference group (C-/S-). Regardless of cancer presence, individuals with sleep disorders consistently reported compromised HRQoL. Furthermore, those with cancer and sleep disorders experienced heightened healthcare resource utilization, underscoring the considerable impact of sleep disorders on overall quality of life. The findings of this study address the importance of sleep disorders among cancer patients and their potential implications for cancer care. Healthcare professionals should prioritize screening, education, and tailored interventions to support sleep health in this population.