The objective of this study was to conduct a detailed analysis of the available flow series in the Chiriquí Viejo River basin in Panama. This paper examines the patterns of variation within these series and calculates various hydrological indexes indicative of the region’s hydrology. Utilizing advanced hydrological indexes within the Chiriquí Viejo River basin in Panama, which spans an area of 1376 km2 and supports an estimated population of 100,000 inhabitants, analytical methods were employed to compute indexes such as the Daily Flow Variation Index (QVAR), the Slope of the Flow Duration Curve (R2FDC), the Hydrological Regulation Index (IRH), and the average duration of low (DLQ75) and high (DHQ25) flow pulses. The results indicate moderate flow variability (QVAR of 0.72) and a Hydrological Regulation Index (IRH) of 2.32, signifying a moderate capacity for flow regulation. Notably, low flow events (DLQ75) lasted approximately 3.73 days, while high flow events (DHQ25) lasted around 4.08 days. The study highlights a significant capacity to respond to extreme events, with maximum annual flows reaching 80.25 m3/s and minimum flows dropping to 3.01 m3/s. Despite the significant contribution of the basin to hydroelectric power generation and other economic activities, there is an observed need for sustainable management that accommodates hydrological fluctuations and promotes resource conservation. The conclusions indicate that these findings are critical for future planning and conservation strategies in the region, emphasizing the importance of integrating multidisciplinary approaches for Hydro-Social Sustainability. This novel and holistic approach underscores the interdependence between hydrological dynamics, socio-economic activities, and environmental sustainability, aiming to ensure the long-term resilience of the Chiriquí Viejo basin and its communities.