Out-of-pocket expenditure (OOPE) directly reflects households’ financial burden for healthcare. Despite efforts to enhance accessibility and affordability through government initiatives and insurance schemes, OOPE remains problematic, especially in rural areas with inadequate public healthcare infrastructure. This study examines factors influencing OOPE in Karnataka’s Dakshina Kannada, Udupi, and Shimoga districts, investigating socioeconomic characteristics, healthcare infrastructure, and accessibility to inform policies for equitable healthcare access and reduced household financial strain. Using purposive sampling, 61 semi-structured interviews were conducted in rural and urban South Karnataka, recorded in Kannada after obtaining consent, and thematically analyzed. Results revealed mixed perceptions of healthcare quality, cost, and accessibility between government and private hospitals. Government facilities were lauded for improved infrastructure and affordability, while private hospitals were preferred for quality and personalized care despite higher costs. Health insurance significantly impacted OOPE reduction. Participants emphasized the need for increased awareness of government insurance programs and improved quality in public hospitals. The study concludes that private hospitals are favored for superior care despite expenses, while government hospitals are valued for affordability. Expanding insurance coverage and improving public awareness are crucial for enhancing healthcare accessibility and affordability.