Background The advent of next-generation computed tomography (CT)- and magnetic resonance imaging (MRI) opened many new perspectives in the evaluation of tumor characteristics. An increasing body of evidence suggests the incorporation of quantitative imaging biomarkers into clinical decision-making to provide mineable tissue information. The present study sought to evaluate the diagnostic and predictive value of a multiparametric approach involving radiomics texture analysis, dual-energy CT-derived iodine concentration (DECT-IC), and diffusion-weighted MRI (DWI) in participants with histologically proven pancreatic cancer. Methods In this study, a total of 143 participants (63 years ± 13, 48 females) who underwent third-generation dual-source DECT and DWI between November 2014 and October 2022 were included. Among these, 83 received a final diagnosis of pancreatic cancer, 20 had pancreatitis, and 40 had no evidence of pancreatic pathologies. Data comparisons were performed using chi-square statistic tests, one-way ANOVA, or two-tailed Student’s t-test. For the assessment of the association of texture features with overall survival, receiver operating characteristics analysis and Cox regression tests were used. Results Malignant pancreatic tissue differed significantly from normal or inflamed tissue regarding radiomics features (overall P < .001, respectively) and iodine uptake (overall P < .001, respectively). The performance for the distinction of malignant from normal or inflamed pancreatic tissue ranged between an AUC of ≥ 0.995 (95% CI, 0.955–1.0; P < .001) for radiomics features, ≥ 0.852 (95% CI, 0.767–0.914; P < .001) for DECT-IC, and ≥ 0.690 (95% CI, 0.587–0.780; P = .01) for DWI, respectively. During a follow-up of 14 ± 12 months (range, 10–44 months), the multiparametric approach showed a moderate prognostic power to predict all-cause mortality (c-index = 0.778 [95% CI, 0.697–0.864], P = .01). Conclusions Our reported multiparametric approach allowed for accurate discrimination of pancreatic cancer and revealed great potential to provide independent prognostic information on all-cause mortality.