This study examines the Vertical Total Electron Content (VTEC) estimation performance of multi-instruments on a global scale during different ionospheric conditions. For this purpose, GNSS-based VTEC data from Global Ionosphere Maps (GIMs), COSMIC (F7/C2)—Feng–Yun 3C (FY3C) radio occultation (RO) VTEC, SWARM–VTEC, and JASON–VTEC were utilized. VTEC assessments were conducted on three distinct days: geomagnetic active (17 March 2015), solar active (22 December 2021), and quiet (11 December 2021). The VTEC values of COSMIC/FY3C RO, SWARM, and JASON were compared with data retrieved from GIMs. According to the results, COSMIC RO–VTEC is more consistent with GIM–VTEC on a quiet day (the mean of the differences is 4.38 TECU), while the mean of FY3C RO–GIM differences is 7.33 TECU on a geomagnetic active day. The range of VTEC differences between JASON and GIM is relatively smaller on a quiet day, and the mean of differences on active/quiet days is less than 6 TECU. Besides the daily comparison, long-term results (1 January–31 December 2015) were also analyzed by considering active and quiet periods. Results show that Root Mean Square Error (RMSE) values of COSMIC RO, FY3C RO, SWARM, and JASON are 5.02 TECU, 6.81 TECU, 16.25 TECU, and 5.53 TECU for the quiet period, and 5.21 TECU, 7.07 TECU, 17.48 TECU, and 5.90 TECU for the active period, respectively. The accuracy of each data source was affected by solar/geomagnetic activities. The deviation of SWARM–VTEC is relatively greater. The main reason for the significant differences in SWARM–GIM results is the atmospheric measurement range of SWARM satellites (460 km–20,200 km (SWARM A, C) and 520 km–20,200 km (SWARM B), which do not contain a significant part of the ionosphere in terms of VTEC estimation.