This study aimed to assess the cost-utility and budget impact of dual to single HER2 targeted neoadjuvant therapy for HER2-positive breast cancer in Sri Lanka. A five-health state Markov model with lifetime horizon was used to assess the cost-utility of neoadjuvant trastuzumab (T) plus pertuzumab (P) or lapatinib (L) compared to single therapy of T with chemotherapy (C), in public healthcare system and societal perspectives. Input parameters were estimated using local data, network meta-analysis, published reports and literature. Costs were adjusted to year 2021 (1USD = LKR194.78). Five-year budget impact for public healthcare system was assessed. Incremental cost-effectiveness ratios in societal perspective for neoadjuvantLTC plus adjuvantT (strategy 3), neoadjuvantPTC plus adjuvantT (strategy 2), neoadjuvantLTC plus adjuvantLT (strategy 5), and neoadjuvantPTC plus adjuvantPT (strategy 4) compared to neoadjuvantTC plus adjuvantT (strategy 1) were USD2716, USD5600, USD6878, and USD12127 per QALY gained, respectively. One GDP per-capita (USD3815) was considered as the cost-effectiveness threshold for the analysis. Even though only the ICER for strategy 3 was cost-effective, uncertainty of efficacy parameter was revealed. For strategy 2 neoadjuvant PTC plus adjuvant T, a 25% reduction of neoadjuvant regimen cost was required to be cost effective for use in early HER2 positive breast cancer.