Climate change poses challenges to infrastructure resilience in Southeast Asia’s flood-prone regions. This study identifies and evaluates strategies for enhancing infrastructure resilience through wastewater treatment plants (WWTPs) in Singapore, Malaysia, Thailand, and Indonesia. Using a mixed-method approach, we analyzed the case studies and conducted quantitative assessments of flood mitigation efforts. Data were collected (2021–2024) through site visits, interviews with key stakeholders, and analysis of historical flood and infrastructure performance data. Data analysis involved statistical methods for assessing their effectiveness and comparative analyses across them. Singapore reduced flood-prone areas by 30% using integrated WWTP technologies with drainage systems, while Malaysia developed resilient infrastructure networks with WWTPs designed to withstand extreme weather, preventing 85% of contamination cases. Thailand combined green and blue infrastructure with WWTPs, decreasing flood vulnerability by 25%. Indonesia invested in decentralized WWTPs in urban areas, increasing infrastructure resilience by 40%. Nature-based solutions, such as ecological restoration, reduce flooding impacts by 20%. The implications for policymakers and practitioners include the need to integrate advanced technologies and nature-based solutions to bolster infrastructure resilience and mitigate flooding risks. This study offers insights into developing effective climate change adaptation strategies in flood-vulnerable regions, emphasizing the critical role of WWTPs in enhancing infrastructure resilience.