Meloidogyne enterolobii is an extremely important plant parasitic nematode. Tomato (Solanum lycopersicum) is an essential worldwide vegetable, and M. enterolobii poses a major threat to its production. The present research investigated the effects of different levels of inoculum density of M. enterolobii (100, 500, 1000, 1500, and 2000 second-stage juveniles (J2s)/plant) on tomato growth, physiological, and biochemical changes at 7, 14, 21, and 28 days post-inoculation (dpi). The negative impact of M. enterolobii on plants gradually increased when the inoculum level increased. Therefore, M. enterolobii population densities (500–2000 J2s/plant) significantly (p < 0.05) reduced plant growth, photosynthetic pigmentation, gas exchange, and chlorophyll fluorescence compared to control plants, while the low population density (100 J2s/plant) showed very little influence. Furthermore, plants with the highest M. enterolobii inoculum (2000 J2s/plant) exhibited a greater number of egg masses and galls. The inoculum densities of M. enterolobii exhibited a notable correlation with the significant elevation of both malondialdehyde (MDA) and hydrogen peroxide (H2O2) levels, which are recognized as very detrimental stresses in plants. Similarly, a rise in the activity of several defensive antioxidant enzymes, namely superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), indicates the defensive mechanism used to combat the oxidative destruction produced by M. enterolobii. The specific activity of glutathione (GSH) and ascorbate (ASA) increased as potent antioxidant defense molecules in response to induced oxidative damage. In addition, our findings also demonstrated that the highest population density (2000 J2s/plant) increased the secondary metabolites responsible for scavenging oxidative stress in the plants. However, further research is required to explore the underlying reasons for this phenomenon and to develop efficient chemical or biocontrol strategies for managing M. enterolobii.