A systematic review and meta-analysis was conducted to determine the effects of resistance training under hypoxic conditions (RTH) on muscle hypertrophy and strength development. Searches of PubMed-Medline, Web of Science, Sport Discus and the Cochrane Library were conducted comparing the effect of RTH versus normoxia (RTN) on muscle hypertrophy (cross sectional area (CSA), lean mass and muscle thickness) and strength development [1-repetition maximum (1RM)]. An overall meta-analysis and subanalyses of training load (low, moderate or high), inter-set rest interval (short, moderate or long) and severity of hypoxia (moderate or high) were conducted to explore the effects on RTH outcomes. Seventeen studies met inclusion criteria. The overall analyses showed similar improvements in CSA (SMD [CIs] = 0.17 [− 0.07; 0.42]) and 1RM (SMD = 0.13 [0.0; 0.27]) between RTH and RTN. Subanalyses indicated a medium effect on CSA for longer inter-set rest intervals and a small effect for moderate hypoxia and moderate loads favoring RTH. Moreover, a moderate effect for longer inter-set rest intervals and a trivial effect for severe hypoxia and moderate loads favoring RTH was found on 1RM. Evidence suggests that RTH employed with moderate loads (60–80% 1RM) and longer inter-set rest intervals (≥ 120 s) enhances muscle hypertrophy and strength compared to normoxia. The use of moderate hypoxia (14.3–16% FiO2) seems to be somewhat beneficial to hypertrophy but not strength. Further research is required with greater standardization of protocols to draw stronger conclusions on the topic.