This review discusses targeted nanoparticle-based diagnostic and treatment options for pancreatic ductal adenocarcinoma (PDAC), the most common and deadliest form of pancreatic cancer. PDAC is highly aggressive, with a poor prognosis due to late diagnosis and resistance to conventional therapies. The tumor environment is complex, with dense stroma hindering drug delivery. Nanotechnology offers innovative solutions by enabling targeted drug delivery systems that enhance drug solubility, circulation time, and tumor targeting. Nanoparticles can be engineered to target specific markers on PDAC cells, such as EGFR, VEGFR, and integrins, and can be conjugated with tumor-penetrating peptides to improve intracellular drug delivery. These systems reduce side effects and improve therapeutic efficacy. Two FDA-approved nanoparticle formulations, Onivyde and Abraxane, have shown promise in PDAC treatment. The review also highlights advances in diagnostic methods, including liquid biopsy, extracellular vesicles, proteomics, and circulating cell-free DNA, which offer non-invasive and highly sensitive detection of PDAC. Non-coding RNAs, such as miRNAs, lncRNAs, and circRNAs, are also emerging as potential biomarkers. Additionally, CRISPR-based diagnostics and artificial intelligence are being explored to enhance early detection and treatment. Light-based techniques, such as light-scattering spectroscopy and laser Raman spectroscopy, are being developed for non-invasive pancreatic cancer detection. The microbiome's role in PDAC development is also discussed. Nanoparticles are being used as molecular imaging agents to improve early detection. Treatment options include surgery, chemotherapy, radiation therapy, and immunotherapy, with targeted therapies and nanoparticle-based delivery systems showing promise. The integration of genomic and pathomic data with AI is advancing personalized medicine for PDAC. Overall, nanotechnology is transforming PDAC diagnosis and treatment, offering new strategies to overcome the challenges of this deadly disease.This review discusses targeted nanoparticle-based diagnostic and treatment options for pancreatic ductal adenocarcinoma (PDAC), the most common and deadliest form of pancreatic cancer. PDAC is highly aggressive, with a poor prognosis due to late diagnosis and resistance to conventional therapies. The tumor environment is complex, with dense stroma hindering drug delivery. Nanotechnology offers innovative solutions by enabling targeted drug delivery systems that enhance drug solubility, circulation time, and tumor targeting. Nanoparticles can be engineered to target specific markers on PDAC cells, such as EGFR, VEGFR, and integrins, and can be conjugated with tumor-penetrating peptides to improve intracellular drug delivery. These systems reduce side effects and improve therapeutic efficacy. Two FDA-approved nanoparticle formulations, Onivyde and Abraxane, have shown promise in PDAC treatment. The review also highlights advances in diagnostic methods, including liquid biopsy, extracellular vesicles, proteomics, and circulating cell-free DNA, which offer non-invasive and highly sensitive detection of PDAC. Non-coding RNAs, such as miRNAs, lncRNAs, and circRNAs, are also emerging as potential biomarkers. Additionally, CRISPR-based diagnostics and artificial intelligence are being explored to enhance early detection and treatment. Light-based techniques, such as light-scattering spectroscopy and laser Raman spectroscopy, are being developed for non-invasive pancreatic cancer detection. The microbiome's role in PDAC development is also discussed. Nanoparticles are being used as molecular imaging agents to improve early detection. Treatment options include surgery, chemotherapy, radiation therapy, and immunotherapy, with targeted therapies and nanoparticle-based delivery systems showing promise. The integration of genomic and pathomic data with AI is advancing personalized medicine for PDAC. Overall, nanotechnology is transforming PDAC diagnosis and treatment, offering new strategies to overcome the challenges of this deadly disease.