This review provides a comprehensive overview of the current landscape in pancreatic cancer (PC) screening, diagnosis, and early detection. This emphasizes the need for targeted screening in high-risk groups, particularly those with familial predispositions and genetic mutations, such as BRCA1, BRCA2, and PALB2. This review highlights the sporadic nature of most PC cases and significant risk factors, including smoking, alcohol consumption, obesity, and diabetes. Advanced imaging techniques, such as Endoscopic Ultrasound (EUS) and Contrast-Enhanced Harmonic Imaging (CEH-EUS), have been discussed for their superior sensitivity in early detection. This review also explores the potential of novel biomarkers, including those found in body fluids, such as serum, plasma, urine, and bile, as well as the emerging role of liquid biopsy technologies in analyzing circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomes. AI-driven approaches, such as those employed in Project Felix and CancerSEEK, have been highlighted for their potential to enhance early detection through deep learning and biomarker discovery. This review underscores the importance of universal genetic testing and the integration of AI with traditional diagnostic methods to improve outcomes in high-risk individuals. Additionally, this review points to future directions in PC diagnostics, including next-generation imaging, molecular biomarkers, and personalized medicine, aiming to overcome current diagnostic challenges and improve survival rates. Ultimately, the review advocates the adoption of informatics and AI-driven strategies to enhance early detection, reduce morbidity, and save lives in the fight against pancreatic cancer.