Robust inference of a low-dimensional parameter in a large semi-parametric model relies on external estimators of infinite-dimensional features of the distribution of the data. Typically, only one of the latter is optimized for the sake of constructing a well behaved estimator of the low-dimensional parameter of interest. Optimizing more than one of them for the sake of achieving a better bias-variance trade-off in the estimation of the parameter of interest is the core idea driving the general template of the collaborative targeted minimum loss-based estimation (C-TMLE) procedure. This chapter discusses an implementation/instantiation of the C-TMLE procedure where the optimization is carried out over a set of continuous tuning parameters, like for instance a regularization parameter in a lasso penalty. Under mild assumptions, the resulting TMLE estimator remains asymptotically linear and Gaussian, allowing the construction of confidence regions of given asymptotic levels.