Abstract Purpose This study assesses the potential for vascular-metabolic imaging with FluoroDeoxyGlucose (FDG)–Positron Emission Tomography/Computed Tomography (PET/CT) perfusion to provide markers of prognosis specific to the site and stage of colorectal cancer. Methods This prospective observational study comprised of participants with suspected colorectal cancer categorized as either (a) non-metastatic colon cancer (M0colon), (b) non-metastatic rectal cancer (M0rectum), or (c) metastatic colorectal cancer (M+). Combined FDG-PET/CT perfusion imaging was successfully performed in 286 participants (184 males, 102 females, age: 69.60 ± 10 years) deriving vascular and metabolic imaging parameters. Vascular and metabolic imaging parameters alone and in combination were investigated with respect to overall survival. Results A vascular-metabolic signature that was significantly associated with poorer survival was identified for each patient group: M0colon – high Total Lesion Glycolysis (TLG) with increased Permeability Surface Area Product/Blood Flow (PS/BF), Hazard Ratio (HR) 3.472 (95% CI: 1.441–8.333), p = 0.006; M0rectum – high Metabolic Tumour Volume (MTV) with increased PS/BF, HR 4.567 (95% CI: 1.901–10.970), p = 0.001; M+ participants, high MTV with longer Time To Peak (TTP) enhancement, HR 2.421 (95% CI: 1.162–5.045), p = 0.018. In participants with stage 2 colon cancer as well as those with stage 3 rectal cancer, the vascular-metabolic signature could stratify the prognosis of these participants. Conclusion Vascular and metabolic imaging using FDG-PET/CT can be used to synergise prognostic markers. The hazard ratios suggest that the technique may have clinical utility.