Delayed and missed diagnosis are a persistent barrier to tuberculosis control, partly driven by limitations associated with sputum collection and an unmet need for decentralized testing. Household contact investigation with point-of-care testing of non-invasive specimens like tongue swabs are hitherto undescribed and may be a cost-effective solution to enable community-based active case finding. In-home, molecular point-of-care testing was conducted using sputum and tongue specimens collected from all household contacts of confirmed tuberculosis cases. A health economic assessment was executed to estimate and compare the cost and cost-effectiveness of different in-home, point-of-care testing strategies. Incremental cost effectiveness ratios of strategies utilizing different combination testing algorithms using sputum and/or tongue swab specimens were compared. The total implementation cost of delivering the standard of care for a 2-year period was $84 962. Strategies integrating in-home point-of-care testing ranged between $87 844 - $93 969. The cost-per-test for in-home, POC testing of sputum was the highest at $20·08 per test. Two strategies, Point-of-Care Sputum Testing and Point-of-Care Combined Sputum and Individual Tongue Swab Testing were the most cost-effective with ICERs of $543·74 and $547·29 respectively, both below a $2,760 willingness-to-pay threshold. An in-home, point-of-care molecular testing strategy utilizing combination testing of tongue swabs and sputum specimens would incur an additional 10.6% program cost, compared to SOC, over a 2-year period. The increased sample yield from tongue swabs combined with immediate result notification following, in-home POC testing would increase the number of new TB cases detected and linked to care by more than 800%. Evidence before this study: We searched PubMed for original research published between January 1, 1950 and June 30, 2024 that evaluated the cost-effectiveness of in-home POC molecular testing, as part of HCI strategies for tuberculosis. PubMed search terms used included ["household contact investigation" OR "household contact tracing"] AND "tuberculosis" AND "cost-effectiveness". The search revealed 8 studies, of which one was removed as HCIs were leveraged for the provision of short course preventative therapy and not tuberculosis testing. None of the studies were conducted in South Africa. All seven remaining studies relied on a hub-and-spoke model of sputum collection and transportation with sputum tested at a centralized laboratory facility. Although active case finding strategies like HCIs are endorsed by the WHO to improve early case detection and treatment initiation, limited research has been done to assess its cost-effectiveness in low- and middle-income countries.Added value of this study: To our knowledge, this is the first example of in-home molecular point-of-care (POC) testing as part of HCI. The use of primary data to estimate and compare the incremental cost effectiveness of different combination, in-home testing strategies utilizing alternative sample types equips policy makers with a selection of strategy options to choose from. The tradeoff between sample types with high collection yield and those with increased accuracy becomes evident in the economic analysis, highlighting the need to consider both yield and accuracy in effective clinical decision making and use-case development. The success of in-home, POC tongue swab testing of all contacts, irrespective of symptom presentation shows great promise for universal testing programs.Implications of all available evidence: Results from our economic modeling provide evidence in support for the integration of in-home, POC tuberculosis (TB) testing during HCI. The use of less invasive tongue swab samples to increase sample yield in the absence of sputum expectoration highlights the value of combination testing strategies. Immediate result notification resulting from rapid, in-home POC testing shows great promise for increasing early case detection and improving treatment uptake. In-home, POC testing strategies, when incorporated into HCI could curb ongoing community transmission and reduce the overall burden of TB. Considerations for adopting novel POC testing strategies in future active case finding programs like HCI should strongly be considered. We evaluated the cost-effectiveness of in-home, point-of-care TB testing of household contacts. The findings indicate that combined testing strategies using tongue swab and sputum specimens could significantly increase TB case detection, with modest additional program costs.