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Increasing regulations and restrictions regarding on-farm chemical use and growing consumer demands for organic food products warrant the development of efficient biological methods for plant disease control and pest management. Grafting and anaerobic soil disinfestation are two sustainable crop production techniques developed to control and regulate weeds, root-knot nematodes (Meloidogyne incognita), and soilborne pathogens. Therefore, the present study explores the economic impact of using grafting and anaerobic soil disinfestation, independently and in conjunction, to determine the best combination in terms of yield and net returns for producers. This study drew from tomato (Solanum lycopersicum) field trials conducted in 2020 on a 0.5-acre plot at the Clemson Coastal Research and Education Center in Charleston, SC, where five grafting and three anaerobic soil disinfestation treatments were used in combinations for comparisons. Each treatment combination was subjected to sealed (plastic mulch covering a plot punctured 5 weeks after applying anaerobic soil disinfestation treatment) and unsealed (plastic mulch covering a plot punctured immediately after the application of anaerobic soil disinfestation treatment) plot conditions during the anaerobic soil disinfestation phase of plant bed preparation. Treatment combinations with cottonseed meal carbon-sourced anaerobic soil disinfestation were unviable because of lower net returns compared with treatment combinations without anaerobic soil disinfestation in nearly every case. Grafting (‘Roadster’ self-grafted) combined with molasses and chicken manure carbon-sourced anaerobic soil disinfestation under unsealed plot conditions was the most optimal treatment combination in the field trials with the greatest gains (net return per acre) to producers. The positive synergistic effects of combining these methods suggest that grafting and anaerobic soil disinfestation yield better results in conjunction than separately.