The soil-borne fungus Fusarium oxysporum (Fo) and the nematode Meloidogyne incognita (Mi) are destructive pathogens that cause substantial yield losses to tomato (Solanum lycopersicum L.) crops worldwide. The present study sought to elucidate the physiological, biochemical, and cytological responses of tomato cultivars (Gailing maofen 802 and Zhongza 09) by root invasion of Fo (1 × 105 CFUmL−1) and Mi (1500 second-stage juveniles (J2) alone and in combination after 14 days. Results revealed that combined inoculation of Fo and Mi significantly increased disease intensity, electrolyte leakage, and hydrogen peroxide and malondialdehyde contents; and decreased photosynthetic capacity and enzyme activity in both cultivars as compared to their solo inoculation. Increasing the disease intensity reduced the maximum morphological traits, such as shoot length, total dry weight, and total chlorophyll contents, in G. maofen 802 (by 32%, 54.2%, and 52.3%, respectively) and Zhongza 09 (by 18%, 32%, and 21%, respectively) as compared to the control. Others factors were also reduced in G. maofen 802 and Zhongza 09, such as photosynthetic capacity (by 70% and 57%, respectively), stomatal conductance (by 86% and 70%, respectively), photochemical quantum yield of photosystem II (YII) (by 36.6% and 29%, respectively), and electron transport rate (by 17.7% and 10%, respectively), after combined inoculation of Fo and Mi. Furthermore, the combined infestation of Fo and Mi resulted in reduced activity of plant-defense-related antioxidants in G. maofen 802 compared with their single application or control. However, these antioxidants were highly up-regulated in Zhongza 09 (by 59%–93%), revealing the induction of tolerance against studied pathogens. The transmission electron microscopy (TEM) results further demonstrated that root cells of Zhongza 09 had unique tetrahedral crystal-like structures in the membrane close to mitochondria under all treatments except control. Therefore, it is concluded that Mi caused severe root damage, suppressed plant growth, depleted antioxidants, and caused high generation of ROS in the presence of Fo as compared to its solo inoculation. Tolerant cultivars adopted different mechanistic strategies at the structural and cellular levels to tolerate the Mi and Fo stresses.