Guava (Psidium guajava) ensures India’s nutritional security by satisfying the dietary needs of people and is cultivated all over the world due to its nutritional and economic importance. In many cases, guava was found susceptible to various pests, diseases, and nematodes. Among them, Root-knot nematode (RKN) is the devastating nematode infesting guava. The guava orchard of MITCAT Farm, Musiri, TN was found to suffer severe yield loss and loss of trees. A study was conducted to find an effective management strategy against RKN in guava at MITCAT guava orchard. Random sampling was carried out in the MITCAT Farm orchard and the nematode was identified as Meloidogyne enterolobii and the infestation was found to be above the Economic Threshold Level (> 2 J2s/g of soil). For the management of this nematode, an in vitro study was carried out using plant extracts and plant extracts with cow urine as it contains antagonistic and nematicidal properties. Among all 11 treatments, Neem + Cow urine showed good efficacy followed by Calotropis + Cow urine which gave minimum egg hatching and maximum juvenile mortality. The best treatment was Neem + Cow urine along with chemical and biocontrol management methods were adopted in field study and standardized the effective management strategies. Six treatments were fixed including the control and healthy control and assessed the initial and final population before and after the treatment. Based on the experimental results, chemical treatment Nimitz showed better performance by reducing half of the nematode population, followed by Velum Prime. The biocontrol agent, Pochonia chlamydosporia, and Neem + Cow urine are on par with each other and exhibited less performance than the chemical nematicide. In conclusion, the application of Nimitz is recommended for the control of M. enterolobii when the infestation is above ETL and is also found to be cost-effective. Whereas either P. chlamydosporia or Neem + Cow urine can be recommended for cases below ETL.