En route travel time estimation (ER-TTE) focuses on predicting the travel time of the remaining route. Existing ER-TTE methods always make re-estimation which significantly hinders real-time performance, especially when faced with the computational demands of simultaneous user requests. This results in delays and reduced responsiveness in ER-TTE services. We propose a general efficient framework U-ERTTE combining an Uncertainty-Guided Decision mechanism (UGD) and Fine-Tuning with Meta-Learning (FTML) to address these challenges. UGD quantifies the uncertainty and provides confidence intervals for the entire route. It selectively re-estimates only when the actual travel time deviates from the predicted confidence intervals, thereby optimizing the efficiency of ER-TTE. To ensure the accuracy of confidence intervals and accurate predictions that need to re-estimate, FTML is employed to train the model, enabling it to learn general driving patterns and specific features to adapt to specific tasks. Extensive experiments on two large-scale real datasets demonstrate that the U-ERTTE framework significantly enhances inference speed and throughput while maintaining high effectiveness. Our code is available at https://github.com/shenzekai/U-ERTTE .