Objective: Obesity, inflammation, and circulating 25-hydroxyvitamin D (25-OHD) have distinct roles in cancer prognosis. The interplay of these factors was investigated by evaluating the associations of body mass index (BMI) with circulating 25-OHD levels in cancer survivors and determining whether associations were modified by inflammation, defined by C-reactive protein (CRP) levels. Methods: Data on cancer survivors were aggregated from the US National Health and Nutrition Examination Survey (2001–2010). Multivariable linear regression models were used to evaluate the associations of BMI with circulating 25-OHD. Analyses were stratified by CRP levels: low < 1.0 mg/L, moderate 1.0-3.0 mg/L, and high > 3.0-9.9 mg/L. Results: Among 1,305 cancer survivors (mean age = 60.8 years, mean BMI = 28.0 kg/m2), circulating 25-OHD levels were 8.74 nmol/L lower (95% CI: 4.71 to 12.77) in cancer survivors with BMI ≥ 30.0 kg/m2 compared with those with BMI < 25.0 kg/m2. This association was, however, limited to those with moderate CRP (−9.90 nmol/L, 95% CI: −16.45 to −3.36) and high CRP (−11.61 nmol/L, 95% CI: −18.71 to −5.05), but not among those with low CRP levels (−5.31 nmol/L, 95% CI:−12.66 to 2.04). Conclusions: A greater understanding of the interplay between 25-OHD and inflammation in cancer survivors with obesity should allow for targeted secondary prevention and help improve prognosis in these patients.