Objective To analyze the effect of rehabilitation nursing and continuous vacuum sealing drainage (VSD) on patients with large area wound and skin tissue defect and its effect on wound healing. Methods A total of 70 patients with large area wounds and skin tissue defects admitted to our hospital from June 2021 to May 2023 were randomly divided into control group and observation group, with 35 patients in each group. The control group was given routine nursing combined with VSD technology, and the observation group was given rehabilitation nursing combined with VSD technology. The wound recovery effect, bacterial infection of wound secretions, prognostic indicators and satisfaction were compared between the two groups. Results The scores of wound recovery in the observation group were higher than those in the control group (P <0.05). After intervention, the bacterial count in the observation group was lower than that in the control group, and the levels of HA and VEGF were higher than those in the control group (P <0.05). The wound healing time and hospitalization time of the observation group were shorter than those of the control group (P <0.05). The satisfaction rate of the observation group was 97.14%, which was higher than 80.00% of the control group (P <0.05). Conclusion Rehabilitation nursing combined with VSD technology has a definite application effect in patients with large area wound and skin tissue defect. It can play a protective role in large area wound and skin tissue defect, reduce inflammatory reaction, promote wound healing as soon as possible, and improve patient satisfaction, which is worthy of clinical application.