A semi-regional study was carried out in the Yaounde-Sangmelima area, a densely vegetated tropical region of southern Cameroon located in the Central Africa Fold Belt (CAFB)/Congo Craton (CC) transition zone. Towards structural lineaments and predictive hydrothermal porphyry deposits mapping, an integrated analysis of Landsat-8 OLI data, aeromagnetic, geological and mineral indices maps was performed. The Remote sensing using False colour composite images involving bands combinations and Crosta method (features oriented principal components analysis) enabled the mapping of the gneisses and schists domains without a clear differentiation between the Yaounde and Mbalmayo schists; despite the reflectance anomalies evidenced NW of Akonolinga, hydrothermal alterations in the study area failed to be detected. Besides, aeromagnetics depicted a moderately fractured northern zone (the CAFB) contrasting with a high densely fractured zone (the CC, known as Ntem complex). The Ntem complex displays signatures of a meta-igneous, an intrusive complex, greenstone relics south of Sangmelima and hydrothermal activity. Indeed, CET porphyry analysis tool detected many porphyry centres. In general, the study revealed many lineaments including contacts, fractures faults zones and strike-slips. The major aeromagnetics structures are SW-NE to WSW-ENE and WNW-ESE to NW-SE while those from Landsat-8 are NE-SW, WNW-ESE, NW-SE, WSW-ENE and NW-ESE to NNW-SSE. Together, these structures depict trans-compressions or trans-tensions corresponding to a broad NE-SW strike-slips channel that affect both the CAFB and the Ntem Complex, and they control the intrusions thus confirming a pervasive hydrothermal activity within the Ntem Complex. The proximity or coincidence of these porphyry centres with some mapped Iron-Gold affiliated mineral indices and porphyry granites indicate the possible occurrence of many hydrothermal ore deposits. These results show the high probability for the Ntem complex to host porphyry deposits so they may serve to boost mineral exploration in the Yaounde-Sangmelima region and in the entire southern Cameroon as well.