This study aims to examine youth players’ physiological responses and technical-tactical performance when playing simulated 3x3 and 5x5 basketball games. Fifteen well-trained male basketball players (16.6 ± 0.2 years old) participated in scrimmage basketball games under two different conditions: 3x3 (half-court) and 5x5 (full-court). The players’ heart rate, muscle oxygen saturation and total hemoglobin data were collected and computed to describe physiological responses, while video analysis was used to characterize their technical-tactical performance. A Bayesian one-way analysis of variance (ANOVA) was used to quantify the predictive influence of both game conditions on the physiological and the technical-tactical variables. The results indicated that different game conditions influenced the players’ physiological responses slightly, as only hemoglobin sample entropy increased between the 3x3 and 5x5 game scenarios. Conversely, statistical differences in most of the technical-tactical variables were moderate and decisive in favour of the game condition model. Overall, this study emphasizes that playing 3x3 and 5x5 basketball games lead to relatively negligible differences in the players’ physiological response but pronounced variations in their technical-tactical performance. Therefore, important implications may be drawn to the applied field as the specificity of technical-tactical adaptations when playing 3x3 or 5x5 formats should be considered by basketball coaches to better design the training sessions for players that fall within our sample age category.