Abstract: This paper proposes the performance assessment of a multi-variable system with multiple time-variant disturbances based on combined left/right diagonal interactor's multi-variable time-variant minimum variance (CMTMV). First, the combined left/right diagonal interactors are introduced into a multi-variable system to characterize the input-output time delay structure. A multi-variable controller is designed based on the CMTMV method, combined with multi-model mixing weights for each time-variant disturbance. Then, each controlled variable output variance is drawn from the multi-variable CMTMV controller. The average variance of all controlled variables is utilized as the benchmark to assess the performance of the multi-variable system with time-variant disturbances. A simulation of the heavy oil distillation process and a numerical case proved the validity of the multi-variable CMTMV performance assessment method.