Background and aim: Adopting the elements of the Serious Game framework has been hypothesised as a strategy to promote the efficacy of social emotional computer-based interventions (CBI) for autistic individuals. This systematic review aimed to review the application of Serious Game principles in current social emotional CBI targeting autistic individuals and evaluate the effect of these principles in remediating social emotional outcomes via meta-analysis. Methods: Database searches identified 34 studies evaluating social emotional CBI with 17 controlled efficacy studies included in meta-regressions analyses. Narrative synthesis summarised the attributes of each CBI based on the five Serious Game principles; motivating storyline, goal directed learning, rewards and feedback, increasing levels of difficulty and individualisation. Results: Based on the scores of the Serious Game assessment tool we developed, findings revealed on average a limited (45%) integration of Serious Game design principles in social emotional CBI for autistic individuals. Main findings from the meta-regressions of 17 controlled efficacy studies revealed a moderating effect of Serious Game design principles on the distant generalisation of social emotional skills and transferability of outcomes among autistic individuals. No significant moderating effects of Serious Game was found for close generalisation and maintenance outcomes. Conclusion: Overall, findings suggest that the Serious Game design framework has utility in guiding the development of social emotional CBI which improve the social emotional skills of autistic individuals.