An infection surveillance system based on a hospital's digital twin [4D-Disease Outbreak Surveillance System (4D-DOSS)] is being developed in Singapore. It offers near-real-time infection surveillance and mapping capabilities. This early economic modelling study was conducted, using meticillin-resistant Staphylococcus aureus (MRSA) as the pathogen of interest, to assess the potential cost-effectiveness of 4D-DOSS. A Markov model that simulates the likelihood of MRSA colonization and infection was developed to evaluate the cost-effectiveness of adopting 4D-DOSS for MRSA surveillance from the hospital perspective, compared with current practice. The cycle duration was 1 day, and the model horizon was 30 days. Probabilistic sensitivity analysis was conducted, and the probability of cost-effectiveness was reported. Scenario analyses and a value of information analysis were performed. In the base-case scenario, with 10-year implementation/maintenance costs of 4D-DOSS of $0, there was 68.6% chance that 4D-DOSS would be cost-effective. In a more pessimistic but plausible scenario where the effectiveness of 4D-DOSS in reducing MRSA transmission was one-quarter of the base-case scenario with 10-year implementation/maintenance costs of $1 million, there was 47.7% chance that adoption of 4D-DOSS would be cost-effective. The value of information analysis showed that uncertainty in MRSA costs made the greatest contribution to model uncertainty. This early-stage modelling study revealed the circumstances for which 4D-DOSS is likely to be cost-effective at the current willingness-to-pay threshold, and identified the parameters for which further research will be worthwhile to reduce model uncertainty. Inclusion of other drug-resistant organisms will provide a more thorough assessment of the cost-effectiveness of 4D-DOSS.