The study aimed to compare the cost-effectiveness of various strategies for screening for MASLD-related advanced hepatic fibrosis (fibrosis stage > 2) using the fibrosis-4 index (FIB-4) and liver stiffness measurement (LSM) by transient elastography (TE) in persons with obesity. We created a decision-analytic model comparing three screening strategies: no screening, TE, and FIB-4 followed by TE. We used a Markov transition model to track liver state, with prevalence and transition probabilities specific to the population with obesity. If MASLD was detected, patients were treated with resmetirom. We found an incremental cost-effectiveness ratio (ICER) of $234,781 (95% CI: $232,581, $235,608) when comparing TE to no screening with a 10-year interval. We note the ICER of $234,673 (95% CI: $234,033, $235,072) when comparing TE to FIB-4+TE. In multivariate simulations, we found no screening was most likely to be cost-effective for willingness-to-pay for QALY below approximately $250,000. Our results suggest routine screening for MASLD in obesity clinics is not cost-effective with resmetirom as the available treatment. A prescreening with FIB-4 before TE did not increase economic efficiency.