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Carcinoembryonic antigen (CEA) and C-reactive protein (CRP) are biomacromolecules known as cancer and inflammatory markers. Thus, they play a crucial role in early cancer diagnosis, post-treatment recurrence detection, and tumor risk assessment. This paper describes the development of an ultrasensitive and selective imprinted paper-based analytical device (PAD) as impedance sensor for determination of CEA and CRP in serum samples for point-of-care testing (POCT). They combine a core comprising of silica nanospheres decorated with silver nanoparticles (SiO 2 @AgNPs) coated with molecularly imprinted polymers (MIPs) for CEA and CRP as shells. CEA-MIP and CRP-MIP were successful coated on the core via self-assembly of N-acetyl-L-cysteine (NAC) followed by building up recognition sites in iminodiacetic acid/ethylene glycol dimethacrylate (IDA/EGDMA) polymer. We constructed a selective and compact imprinted PAD based on a SiO 2 @AgNPs@MIP-CEA- and SiO 2 @AgNPs@MIP-CRP-modified graphene electrode, a so-called Dual-C sensor. The resulting twin voltammetric cells to detect CEA and CRP use foldable hydrophobic back-up sheets acting as reservoirs. The advantages of this approach include straightforward manufacturing with highly reproducibility, quick assembly, and good physical durability. The Dual-C sensor revealed excellent linear dynamic ranges of 0.0001 to 10 ng mL -1 for both CEA and CRP, which covers on the concentration ranges of clinical interest for both analytes. Furthermore, the system shows high accuracy and precision, with no evidence of interference from serum samples., Competing Interests: Declarations. Ethical approval: The research was conducted in accordance with the Declaration of Helsinki and approved by the Human Research Ethics Committee of Ubon Ratchathani University. The committee confirmed that the proposed study aligns with international ethical standards, as well as with applicable laws, regulations, and national requirements. The research was approved under certification number UBU-REC-20/2567. Serum samples from cancer patients, with histopathologically confirmed diagnoses, were obtained with permission from the Ethical Committee of Ubon Ratchathani Cancer Hospital, Thailand (No. EC-10/2024). Consent to participate: Informed consent was obtained from all individual participants included in the study. All participants were fully informed about the nature of the research and voluntarily agreed to participate. Conflicts of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)