In this experimental study, picosecond laser treatment was performed on a nickel-based superalloy Nimonic 263, aiming to investigate the surface effects induced by irradiation in different atmospheric conditions and, concerning changes in surface composition, regarding the possibility for improvement of its functionality. Besides the varying laser parameters, such as a number of pulses and pulse energy, environmental conditions are also varied. All surface modifications were carried out in standard laboratory conditions and a nitrogen- and argon-rich atmosphere. The resulting topography effects depend on the specific laser treatment and could be categorized as increased roughness, crater formation, and formation of the laser-induced periodic surface structures (LIPSS). Changes in the chemical surface composition are distinguished as the potential formation of the protective oxides/nitrides on the sample surface. Numerous characterization techniques analyse the resulting effects on the topography and surface parameters. The multi-response parametric optimization of the picosecond laser process was performed using an advanced statistical method based on Taguchi’s robust parameter design. Finally, the optimal parameter conditions for Nimonic 263 modification are suggested.