Background: The level of effort seems to play a key role in determining neuromuscular adaptations; however, less is known regarding the optimal dose-response for intra-set levels of effort on chronic resistance training (RT) adaptations. Objective: We aimed to synthesize the current literature on chronic RT adaptations in response to different intra-set velocity loss (VL) thresholds in the back squat exercise. We investigated changes in muscle strength, muscular endurance, sports-related physical performance, and muscle hypertrophy outcomes during resistance exercise to establish optimal dose-response relationships in physically active individuals.Methods: We conducted a literature search using PubMed (Medline), Web of Science™, Scopus, and Cochrane up to April 2021, with no restriction on year of publication. The inclusion criteria were based on the PICO strategy. A random-effect meta-analysis was performed to determine the standardized mean differences (SMD ± 95% confidence intervals) for different intra-set VL thresholds (low VL [< 15%], moderate VL [≥ 15% and < 30%], and high VL [≥ 30%]) in RT on maximum muscular strength, bar velocity against submaximal loads, endurance against a given load, countermovement jump height, running sprint time, and muscle hypertrophy. Results: A total of 4,031 articles were found and 11 studies met our eligibility criteria. Pooled results revealed improvements between pre- and post-training intervention in 1RM strength (SMD = 0.78; p < 0.001); bar velocity outputs (light-loads [SMD = 0.79; p < 0.001] and heavy-loads [SMD = 2.08; p < 0.001]); endurance against a given load (SMD = 1.21; p < 0.001); countermovement jump height (SMD = 0.50; p < 0.001); running sprint time (SMD = - 0.28; p = 0.001); and muscle hypertrophy (SMD = 0.31; p = 0.05), with no significant difference between VL thresholds (p > 0.05). However, low VL elicited greater within-group SMD for 1RM strength than moderate and high VL thresholds (SMD = 0.93; 0.72; and 0.75; for low, moderate, and high VL thresholds, respectively). Low and moderate VL thresholds resulted in greater within-group SMD than high VL thresholds for velocity against light loads (SMD for low VL = 0.89; moderate VL = 0.90; high VL = 0.59); countermovement jump height (SMD for low VL = 0.51; moderate VL = 0.58; high VL = 0.36); and running sprint time (SMD for low VL = -0.49; moderate VL = -0.32; high VL = -0.09). Moderate and high VL thresholds induced higher within-group SMD for muscle hypertrophy than low VL (SMD for low VL = 0.14; moderate VL = 0.40; high VL = 0.44). Conclusions: Low to moderate VL thresholds may provide more effective and efficient training stimuli for improving performance in strength-power tasks, due to the similar or even greater chronic adaptations achieved compared with high VL, despite the lower number of repetitions performed during the RT program. Conversely, moderate to high VL may provide more favorable training stimuli for inducing muscle hypertrophy. Strength coaches may apply these dose-response trends to design optimal RT stimuli based on their specific training goals. Protocol registration: The study protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42020189321).