Introduction: Monthly oral HIV pre-exposure prophylaxis (PrEP) such as MK-8527 offer promise as low-cost, self-administered options that are easily delivered through community-based platforms. Economic evaluations of MK-8527 either alone or alongside other long-acting (LA) PrEP products like lenacapavir are needed for informing HIV prevention strategies. Methods: We adapted an agent-based network model, EMOD-HIV, to simulate LA-PrEP scale-up in South Africa and western Kenya from 2026-2035; scenarios evaluated MK-8527 alone, lenacapavir alone and combined strategies, with varying uptake among female sex workers, their male clients, and individuals with >1 partner. We assumed 95% effectiveness of MK-8527 for 2 months (assuming individuals took 2 of 3 pills dispensed) and 95% lenacapavir effectiveness for 6 months. Scenarios were compared to a baseline of daily oral PrEP only. Results: Assuming the same uptake rates, MK-8527 alone achieved lower health impacts than lenacapavir alone in both settings (6-14% vs. 11-18% of HIV infections averted) but had substantially lower costs; provision costs of MK-8527 were 58-59% lower than lenacapavir assuming $1.00/pill and 40-43% lower at $2.50/pill. In western Kenya, ICERs for MK-8527 alone were $467/DALY averted and $799/DALY averted assuming pill prices of $1.00 and $2.50 respectively, compared to $1,306/DALY averted for lenacapavir. In South Africa, all LA-PrEP strategies were cost-saving over the 35-year horizon, although near-term budget impacts were substantial ($169-348 million over five years). Service delivery accounted for the majority of MK-8527 costs (73% at $1.00 per pill). Combined strategies of lenacapavir and MK-8527 increased health benefits (13-23% infections averted) but had higher provision costs than either strategy alone. Conclusion: MK-8527 can reduce HIV incidence at lower costs than lenacapavir. However, high service delivery costs limit its cost-effectiveness to scenarios in which pill prices are low (US$1.00 per pill) and provision is targeted to populations at substantial HIV risk.