To determine the effectiveness of uni- or multimodal prehabilitation on several outcomes in patients undergoing neoadjuvant therapy before cancer surgery. A systematic search was carried on May 1, 2023, using four major databases (SCOPUS, Web of Science, Medline (Ovid and Pubmed)) and updated monthly until February 2024. Inclusion criteria included (i) any original articles (any design), (ii) adult patients undergoing neoadjuvant therapy (NAT) prior to surgical resection, (iii) participation in uni- or multimodal prehabilitation programs during NAT, and (iv) reporting on any functional, treatment-related, or perioperative outcome. Two reviewers independently conducted the search and screened all records. Risk of bias was assessed using the Johanna Briggs Institute Appraisal Tools independently by two reviewers. A random-effects meta-analysis was performed for all outcomes with two or more studies. A total of 30 records met the inclusion criteria and were analyzed. Studies showed that prehabilitation during NAT can be feasible in most settings and increase or prevent the loss of cardiorespiratory fitness (CRF), maintain or improve muscle mass, and improve pathological response and treatment completion compared to no prehabilitation, but the certainty of the evidence is low to moderate. However, according to our findings, prehabilitation has little to no effect on postoperative complications and length of hospital stay as well as in health-related quality of life. Prehabilitation during NAT might be feasible and associated with improvements in cardiorespiratory fitness, muscle mass, and treatment response/completion with low-to-moderate certainty of evidence. Insufficient data on safety is available at this stage.