In a prospective study, photon-counting CT (PCCT) with ultra-high-resolution acquisition was used to determine the optimal combination of slice thickness and virtual monoenergetic imaging (VMI) for the assessment of pancreatic ductal adenocarcinoma (PDAC) and peripancreatic vasculature. A cohort of 74 patients with histologically confirmed PDAC underwent PCCT with reconstruction of multiple ultra-high-resolution image series varying in spatial resolution and monoenergetic levels. Quantitative analysis demonstrated that both tumor-to-pancreas and vessel contrast-to-noise ratios (CNR), as well as signal-to-noise ratios (SNR) increased progressively at lower monoenergetic levels, reaching their maximum at 40 keV (all P < 0.001), while image noise was lowest in 1-mm-thick reconstructions at 70 keV. Qualitative assessment showed that 1-mm-thick images at 70 keV and ultra-thin 0.4-mm reconstructions at low monoenergetic levels (45–50 keV) provided superior diagnostic performance and image quality, particularly in depicting fine pancreatic anatomy and small vascular structures. These findings suggest that PCCT enables image optimization in PDAC imaging and that the combination of ultra-high-resolution with low-keV VMI—particularly around 45 keV—improves preoperative evaluation of tumor extent and resectability.