Current treatment of immature necrotic permanent teeth with a periapical lesion is regenerative endodontics, which is based on tissue engineering under the triade of stem cells, scaffolds and bioactive molecules. This Umbrella Review was aimed to evaluate the success of scaffold and regenerative materials used for the treatment of these teeth, in terms of apical closure, tooth length increase, widening of root canal walls, tissue vitality and periapical lesion repair. An extensive literature research was carried out in the Medline, ISI Web of Science, and Scopus databases for relevant systematic reviews matching the keyword search strategy. Based on inclusion and exclusion criteria, reviewers independently rated the quality of each study to determine their level of evidence. Methodological quality assessment of each article was obtained using A Measurement Tool to Assess Systematic Reviews (AMSTAR)-2 tool, and risk of bias was assessed with the Risk of Bias in Systematic Reviews (ROBIS) tool. After removing duplicates, 155 articles were found; from which 133 were excluded for being non-relevant and 15 other due to exclusion criteria. One more was discarded after methodological quality evaluation, for a total of six articles remaining. The most common scaffold used was the blood clot, others used were poly lactic-co-glycolic acid and platelet-rich fibrin matrix. The most common regeneration material used was Mineral Trioxide Aggregate (MTA), followed by Biodentine. An increase in tooth length and widening of root canal walls were reported in all selected studies with different proportions, as well as periapical lesion repair. ROBIS analysis showed that only one article had low bias, two were classified as unclear bias, while the remaining three had high risk of bias. An exhaustive literature search was carried out applying language filters, high-quality indexed journals, year of publication, which ensures the best quality articles were included. Blood clot was the most used scaffold as is the most easy to place inside the canal and does not require to extract blood from the patient. The use of MTA and Biodentine as sealing materials has been associated with thickening of canal walls, apical closure and reduced signs and symptoms of apical periodontitis. However, most of the included reviews assessed were case reports and only in a few of them were clinical trials included. There is also a lack of risk of bias analysis in most reviews. The blood clot is the most common scaffold used for inducing regeneration during the treatment of immature necrotic teeth. Tooth length increase and widening of root canal walls are the most common criteria used in the studies as success indicators. MTA and Biodentine did not show differences in the results analysed. Quality assessment and bias risk evaluation showed that it is necessary to design better studies with rigorous methodology to recommend a trustable and predictable protocol for the treatment of immature necrotic permanent teeth with periapical lesions. International Prospective Register of Systematic Reviews (PROSPERO) CRD42021248404.