Diaspis echinocacti (Bouché) (Hemiptera: Diaspididae) causes severe damage to Opuntia spp. (Cactaceae) worldwide, necessitating effective control measures. In this study, we tested the single and combined use of predatory ladybirds and a fungal pathogen on D. echinocacti infesting Opuntia ficus-indica (L.) Mill. Plants under screenhouse conditions (mean 26.32 °C, 55.1% RH.). The treatments were: untreated control, 0.003% Tween 80 (TW), Chilocorus bipustulatus (Coleoptera: Coccinellidae) (CB) alone, Exochomus nigripennis (Coleoptera: Coccinellidae) (EN) alone, entomopathogenic fungi Alternaria murispora (AM) alone, AM + CB, AM + EN, and mineral oil (MO) (positive control). Treatment efficacy was evaluated weekly for five weeks. AM + EN and AM + CB treatments significantly reduced egg counts to 4.89 and 2.44 by week 5, respectively. For motile stages, the AM + CB and AM + EN treatments were most effective, reducing counts to 6.89 and 9.56 by week 5. AM alone resulted in the highest number of mummies (D. echinocacti killed by A. murispora) (29.67) by week 5. For predator densities, C. bipustulatus peaked at 36.11 individuals per cladode by week 3 in the CB-only treatment, while E. nigripennis peaked at 32.33 individuals per cladode by week 3 in the EN-only treatment. Both CB and EN densities were higher in single treatments compared to the combined treatments throughout the study. Combining A. murispora with C. bipustulatus or E. nigripennis significantly reduced D. echinocacti infestations on O. ficus-indica without affecting plant quality (visual score >9 by week 5). Prolonged exposure enhanced efficacy, showing promise for effective non-chemical pest management.