Background: Hand, foot, and mouth disease (HFMD) remains a major public-health concern in China. While the monovalent EV-A71 vaccine has effectively reduced EV-A71–associated cases, it offers no protection against CV-A16. The introduction of a bivalent EV-A71/CV-A16 vaccine may offer broader protection, but its economic viability under different immunization strategies remains uncertain. Methods: We developed a dynamic transmission model integrated with cost-effectiveness analysis to assess the epidemiological and economic impact of a hypothetical bivalent EV-A71/CV-A16 vaccine in China. Based on the immunization program policy, seven vaccination strategies, vaccine effectiveness (VE) levels ranging from 50–95% against EV-A71/CV-A16, and coverage levels from 0–95% were evaluated. The threshold vaccine price (TVP) was derived based on incremental cost-effectiveness ratio (ICER) calculations. Cost-effectiveness was assessed using willingness-to-pay (WTP) thresholds defined as 1–3 times the gross domestic product (GDP) per capita. Results: The mean cost of two doses of the monovalent EV-A71 vaccine was USD133.0 (95% CI: 126.9–139.1). Strategy 2, which targeted individuals unvaccinated with the monovalent EV-A71 vaccine, demonstrated the most favorable cost-effectiveness. At 45% coverage and 85% vaccine effectiveness, the estimated threshold price per dose was USD 107.7 (95% CI: 103.4–112.0), with threshold vaccine prices increasing as coverage declined. When vaccination coverage exceeded 80%, the threshold vaccine price decreased substantially, falling below USD 45.9 (95% CI: 43.5–48.3) per dose. Conclusions: Large-scale inclusion in the national immunization program may not be economically justified at current cost levels. Targeted voluntary vaccination of unvaccinated, susceptible populations represents a more cost-effective and practical strategy during the early stage of vaccine introduction.