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Climate change disproportionately impacts vulnerable populations, including children with physical disabilities who face mobility challenges and barriers to accessing essential services. In Nepal, a country highly exposed to climate-related hazards, caregivers are crucial for protecting these children, yet their understanding of climate change remains largely unassessed. This study aimed to evaluate caregivers’ knowledge of climate change among children with physical disabilities in Nepal. A cross-sectional study was conducted among 280 caregivers recruited from the Hospital and Rehabilitation Center for Disabled Children (HRDC) in Banepa and its satellite clinics in three provinces: Bagmati, Koshi, and Lumbini. Data were collected between January and March 2025 using a structured questionnaire and the standardized Climate Change Knowledge Test (CCKT). Descriptive statistics and chi-square tests were used to analyze knowledge levels and their associations with sociodemographic, occupational, and environmental engagement factors. Results showed that 62.2% of caregivers had a moderate to high level of knowledge (37.9% high, 24.3% moderate), while 37.9% had low knowledge. Knowledge levels varied significantly by province of residence (p < 0.001), with Bagmati (62.5% high knowledge) and Koshi (61.1%) outperforming Lumbini (31.9%). Other significant associations included gender (p = 0.001), ethnicity (p < 0.001), education level (p < 0.001), Occupation (p < 0.001), and participation in afforestation (p = 0.002). Education was the strongest predictor; 80% of caregivers with a bachelor’s degree or above had high knowledge, compared to only 8.6% of those with no formal education. Despite 91.1% of caregivers reporting experiencing high temperatures, disaster preparedness was critically low: 95.7% lacked an emergency plan, and 95.0% had never received disaster training. This study reveals significant disparities in climate change knowledge among caregivers of children with physical disabilities in Nepal, strongly influenced by geography, education, and environmental engagement. The findings underscore an urgent need for targeted, inclusive climate education and disaster preparedness programs, particularly for marginalized groups and those in low-performing regions. The results can inform national climate and disability policies to integrate disability-inclusive perspectives, strengthen caregiver capacity, and promote climate resilience for vulnerable children.