Precise accounting of carbon stocks and fluxes in tropical vegetation using remote sensing approaches remains a challenging exercise, as both signal saturation and ground sampling limitations contribute to inaccurate extrapolations. Airborne LiDAR Scanning (ALS) data can be used as an intermediate level to radically increase sampling and enhance model calibration. Here we tested the potential of using ALS data for upscaling vegetation aboveground biomass (AGB) from field plots to a forest-savanna transitional landscape in the Guineo-Congolian region in Cameroon, using either a design-based approach or a model-based approach leveraging multispectral satellite imagery. Two sets of reference data were used: (1) AGB values collected from 62 0.16-ha plots distributed both in forests and savannas; and (2) an AGB map generated form ALS data. In the model-based approach, we trained Random Forest models using predictors from recent sensors of varying spectral and spatial resolutions (Spot 6⁄7, Landsat 8, and Sentinel 2), along with biophysical predictors derived after pre-processing into the Overland processing chain, following a forward variable selection procedure with a spatial 4-folds cross validation. The models calibrated with field plots lead to a systematic overestimation in AGB density estimates and a root mean squared prediction error (RMSPE) of up to 65 Mg.ha−1 (90%), whereas calibration with ALS lead to low bias and a drop of ~30% in RMSPE (down to 43 Mg.ha−1, 58%) with little effect of the satellite sensor used. Decomposing bias along the AGB density range, we show that multispectral images can (in some specific cases) be used for unbiased prediction at landscape scale on the basis of ALS-calibrated statistical models. However, our results also confirm that, whatever the spectral indices used and attention paid to sensor quality and pre-processing, the signal is not sufficient to warrant accurate pixelwise predictions, because of large relative RMSPE, especially above (200–250 t/ha). The design-based approach, for which average AGB density values were attributed to mapped land cover classes, proved to be a simple and reliable alternative (for landscape to region level estimations), when trained with dense ALS samples.